From 0a5ec4d727f8def49239d5ee257bbda51e011fac Mon Sep 17 00:00:00 2001
From: jbloom <jbloom@users.noreply.github.com>
Date: Tue, 24 Sep 2024 18:17:42 +0000
Subject: [PATCH] deploy: 268a1a68ea13a8ed6e6831aebae4b89860282154

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 <span class="line"><span style="--shiki-light:#22863A;--shiki-dark:#85E89D;">Branch to deploy</span><span style="--shiki-light:#24292E;--shiki-dark:#E1E4E8;">: </span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;">main</span></span>
 <span class="line"><span style="--shiki-light:#22863A;--shiki-dark:#85E89D;">Build command</span><span style="--shiki-light:#24292E;--shiki-dark:#E1E4E8;">: </span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;">npm run build</span></span>
 <span class="line"><span style="--shiki-light:#22863A;--shiki-dark:#85E89D;">Publish directory</span><span style="--shiki-light:#24292E;--shiki-dark:#E1E4E8;">: </span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;">.vitepress/dist</span></span></code></pre></div><p>We&#39;ve also configured Netlify to use a custom domain for this website and updated the DNS (<strong>D</strong>omain <strong>N</strong>ame <strong>S</strong>ystem is a set of instructions in a database that connects domain names to IP addresses in DNS servers) by adding the address of the Name Servers hosting our website with Netlify to the Name Servers records on Namecheap.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
-    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-import{_ as s,c as i,o as a,f as e}from"./chunks/framework.B63u0Dcf.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/README.html"}]]},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e(`<h1 id="bloom-lab-website" tabindex="-1"><a href="https://jbloomlab.org/" target="_blank" rel="noreferrer">Bloom Lab Website</a> <a class="header-anchor" href="#bloom-lab-website" aria-label="Permalink to &quot;[Bloom Lab Website](https://jbloomlab.org/)&quot;">​</a></h1><p>This repository contains the code the Bloom Lab&#39;s <a href="https://jbloomlab.org/" target="_blank" rel="noreferrer">public website</a>. The website is based on a custom <a href="https://vitepress.dev/guide/what-is-vitepress" target="_blank" rel="noreferrer">VitePress</a> theme. Using VitePress allows us to take advantage of the VitePress ecosystem for routing and markdown processing.</p><p>Contributions to the website are made by writing markdown documents and editing YAML and JSON configuration files.</p><p>The content of our lab&#39;s website draws inspiration from lab websites like those of <a href="https://bedford.io/" target="_blank" rel="noreferrer">Trevor Bedford</a>, <a href="https://matsen.fhcrc.org/" target="_blank" rel="noreferrer">Erick Matsen</a>, and <a href="https://www.elowitz.caltech.edu/" target="_blank" rel="noreferrer">Michael Elowitz</a>. We also borrow styles from <a href="https://vitepress.dev/guide/what-is-vitepress" target="_blank" rel="noreferrer">VitePress</a> to maintain consistency with our other VitePress websites.</p><h2 id="installation" tabindex="-1">Installation <a class="header-anchor" href="#installation" aria-label="Permalink to &quot;Installation&quot;">​</a></h2><p>Contributions to the lab website are made through <a href="https://github.com/jbloomlab/jbloomlab.github.io" target="_blank" rel="noreferrer">GitHub</a> using pull requests.</p><p>Clone the <code>git</code> repository locally to edit the site:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">git</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> clone</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> https://github.com/jbloomlab/jbloomlab.github.io</span></span>
+import{_ as s,c as i,o as a,f as e}from"./chunks/framework.5XYse7Qj.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/README.html"}]]},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e(`<h1 id="bloom-lab-website" tabindex="-1"><a href="https://jbloomlab.org/" target="_blank" rel="noreferrer">Bloom Lab Website</a> <a class="header-anchor" href="#bloom-lab-website" aria-label="Permalink to &quot;[Bloom Lab Website](https://jbloomlab.org/)&quot;">​</a></h1><p>This repository contains the code the Bloom Lab&#39;s <a href="https://jbloomlab.org/" target="_blank" rel="noreferrer">public website</a>. The website is based on a custom <a href="https://vitepress.dev/guide/what-is-vitepress" target="_blank" rel="noreferrer">VitePress</a> theme. Using VitePress allows us to take advantage of the VitePress ecosystem for routing and markdown processing.</p><p>Contributions to the website are made by writing markdown documents and editing YAML and JSON configuration files.</p><p>The content of our lab&#39;s website draws inspiration from lab websites like those of <a href="https://bedford.io/" target="_blank" rel="noreferrer">Trevor Bedford</a>, <a href="https://matsen.fhcrc.org/" target="_blank" rel="noreferrer">Erick Matsen</a>, and <a href="https://www.elowitz.caltech.edu/" target="_blank" rel="noreferrer">Michael Elowitz</a>. We also borrow styles from <a href="https://vitepress.dev/guide/what-is-vitepress" target="_blank" rel="noreferrer">VitePress</a> to maintain consistency with our other VitePress websites.</p><h2 id="installation" tabindex="-1">Installation <a class="header-anchor" href="#installation" aria-label="Permalink to &quot;Installation&quot;">​</a></h2><p>Contributions to the lab website are made through <a href="https://github.com/jbloomlab/jbloomlab.github.io" target="_blank" rel="noreferrer">GitHub</a> using pull requests.</p><p>Clone the <code>git</code> repository locally to edit the site:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">git</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> clone</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> https://github.com/jbloomlab/jbloomlab.github.io</span></span>
 <span class="line"><span style="--shiki-light:#005CC5;--shiki-dark:#79B8FF;">cd</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> jbloomlab.github.io</span></span></code></pre></div><p>You&#39;ll need to install Javascript and its relevant packages to preview the site as you make changes. You&#39;re going to need two pieces of software to do this: <code>Node.js</code> and <code>npm</code>.</p><p><code>Node.js</code> is an environment that allows you to run Javascript code on your computer. <code>npm</code> is a package manager that contains the Javascript libraries necessary to create the website. The instructions for installing <code>Node</code> and <code>npm</code> depend on your operating system and personal preference.</p><h3 id="without-conda" tabindex="-1">Without <code>conda</code> <a class="header-anchor" href="#without-conda" aria-label="Permalink to &quot;Without \`conda\`&quot;">​</a></h3><p>Follow the instructions <a href="https://docs.npmjs.com/downloading-and-installing-node-js-and-npm" target="_blank" rel="noreferrer">here</a> to install <code>Node</code> without a package manager.</p><h3 id="with-conda" tabindex="-1">With <code>conda</code> <a class="header-anchor" href="#with-conda" aria-label="Permalink to &quot;With \`conda\`&quot;">​</a></h3><p>If you have <code>conda</code> on your operating system, you can use it to install <code>node</code> and <code>npm</code>.</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">conda</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> env</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> create</span><span style="--shiki-light:#005CC5;--shiki-dark:#79B8FF;"> -f</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> environment.yml</span></span>
 <span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">conda</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> activate</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> jbloomlab.github.io</span></span></code></pre></div><h3 id="install-npm-packages-and-view-page" tabindex="-1">Install <code>npm</code> packages and view page <a class="header-anchor" href="#install-npm-packages-and-view-page" aria-label="Permalink to &quot;Install \`npm\` packages and view page&quot;">​</a></h3><p>Regardless of how you installed <code>Node</code> and <code>npm</code>, verify that the installation worked by running:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">node</span><span style="--shiki-light:#005CC5;--shiki-dark:#79B8FF;"> -v</span></span>
 <span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">npm</span><span style="--shiki-light:#005CC5;--shiki-dark:#79B8FF;"> -v</span></span></code></pre></div><p>If this is the first time you&#39;re contributing to the website, you&#39;ll need to tell <code>npm</code> to install all of the packages in the <code>package.json</code> file. To do this, run the following command from within the repository:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">npm</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> install</span></span></code></pre></div><h2 id="developing" tabindex="-1">Developing <a class="header-anchor" href="#developing" aria-label="Permalink to &quot;Developing&quot;">​</a></h2><p>While you&#39;re editing the content of the website, it&#39;s important to see a live preview of your changes. You can do this by booting up a local &quot;development&quot; server to open the local version of the lab website on your browser. To do this, simply run:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#6F42C1;--shiki-dark:#B392F0;">npm</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> run</span><span style="--shiki-light:#032F62;--shiki-dark:#9ECBFF;"> dev</span></span></code></pre></div><p>Now, there will be a local version of the website running at <code>http://localhost:5173</code> (or some other URL printed to the console). Visit this URL in your browser to see a preview of the site.</p><h2 id="contributing" tabindex="-1">Contributing <a class="header-anchor" href="#contributing" aria-label="Permalink to &quot;Contributing&quot;">​</a></h2><p>The general file structure of this website is as follows:</p><div class="language-bash vp-adaptive-theme"><button title="Copy Code" class="copy"></button><span class="lang">bash</span><pre class="shiki shiki-themes github-light github-dark vp-code"><code><span class="line"><span style="--shiki-light:#005CC5;--shiki-dark:#79B8FF;">.</span></span>
diff --git a/assets/README.md.nS8rQRw1.lean.js b/assets/README.md.5t9AtTQ6.lean.js
similarity index 71%
rename from assets/README.md.nS8rQRw1.lean.js
rename to assets/README.md.5t9AtTQ6.lean.js
index be183d8..aa45fe1 100644
--- a/assets/README.md.nS8rQRw1.lean.js
+++ b/assets/README.md.5t9AtTQ6.lean.js
@@ -1 +1 @@
-import{_ as s,c as i,o as a,f as e}from"./chunks/framework.B63u0Dcf.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/README.html"}]]},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e("",65),l=[n];function h(p,o,r,d,k,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default};
+import{_ as s,c as i,o as a,f as e}from"./chunks/framework.5XYse7Qj.js";const E=JSON.parse('{"title":"Bloom Lab Website","description":"","frontmatter":{"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/README.html"}]]},"headers":[],"relativePath":"README.md","filePath":"README.md"}'),t={name:"README.md"},n=e("",65),l=[n];function h(p,o,r,d,k,c){return a(),i("div",null,l)}const y=s(t,[["render",h]]);export{E as __pageData,y as default};
diff --git a/assets/app.B3f_B_nC.js b/assets/app.B3f_B_nC.js
deleted file mode 100644
index 21815ca..0000000
--- a/assets/app.B3f_B_nC.js
+++ /dev/null
@@ -1 +0,0 @@
-import{V as o,W as p,X as u,Y as l,Z as c,$ as f,a0 as d,a1 as m,a2 as h,a3 as A,a4 as g,a5 as P,a6 as _,u as v,B as R,a7 as w,a8 as y,a9 as C,aa as E,ab as b}from"./chunks/framework.B63u0Dcf.js";import{R as T}from"./chunks/theme.DauYRQxa.js";function i(e){if(e.extends){const a=i(e.extends);return{...a,...e,async enhanceApp(t){a.enhanceApp&&await a.enhanceApp(t),e.enhanceApp&&await e.enhanceApp(t)}}}return e}const s=i(T),S=_({name:"VitePressApp",setup(){const{site:e,lang:a,dir:t}=v();return R(()=>{w(()=>{document.documentElement.lang=a.value,document.documentElement.dir=t.value})}),e.value.router.prefetchLinks&&y(),C(),E(),s.setup&&s.setup(),()=>b(s.Layout)}});async function D(){globalThis.__VITEPRESS__=!0;const e=L(),a=V();a.provide(u,e);const t=l(e.route);return a.provide(c,t),a.component("Content",f),a.component("ClientOnly",d),Object.defineProperties(a.config.globalProperties,{$frontmatter:{get(){return t.frontmatter.value}},$params:{get(){return t.page.value.params}}}),s.enhanceApp&&await s.enhanceApp({app:a,router:e,siteData:m}),{app:a,router:e,data:t}}function V(){return h(S)}function L(){let e=o,a;return A(t=>{let n=g(t),r=null;return n&&(e&&(a=n),(e||a===n)&&(n=n.replace(/\.js$/,".lean.js")),r=P(()=>import(n),[])),o&&(e=!1),r},s.NotFound)}o&&D().then(({app:e,router:a,data:t})=>{a.go().then(()=>{p(a.route,t.site),e.mount("#app")})});export{D as createApp};
diff --git a/assets/app.DGeoigqM.js b/assets/app.DGeoigqM.js
new file mode 100644
index 0000000..e09d99f
--- /dev/null
+++ b/assets/app.DGeoigqM.js
@@ -0,0 +1 @@
+import{a3 as o,a4 as p,a5 as u,a6 as l,a7 as c,a8 as f,a9 as d,aa as m,ab as h,ac as g,ad as A,ae as P,af as _,u as v,B as R,ag as w,ah as y,ai as C,aj as E,ak as b}from"./chunks/framework.5XYse7Qj.js";import{R as T}from"./chunks/theme.CECrkTxV.js";function i(e){if(e.extends){const a=i(e.extends);return{...a,...e,async enhanceApp(t){a.enhanceApp&&await a.enhanceApp(t),e.enhanceApp&&await e.enhanceApp(t)}}}return e}const s=i(T),S=_({name:"VitePressApp",setup(){const{site:e,lang:a,dir:t}=v();return R(()=>{w(()=>{document.documentElement.lang=a.value,document.documentElement.dir=t.value})}),e.value.router.prefetchLinks&&y(),C(),E(),s.setup&&s.setup(),()=>b(s.Layout)}});async function D(){globalThis.__VITEPRESS__=!0;const e=L(),a=j();a.provide(u,e);const t=l(e.route);return a.provide(c,t),a.component("Content",f),a.component("ClientOnly",d),Object.defineProperties(a.config.globalProperties,{$frontmatter:{get(){return t.frontmatter.value}},$params:{get(){return t.page.value.params}}}),s.enhanceApp&&await s.enhanceApp({app:a,router:e,siteData:m}),{app:a,router:e,data:t}}function j(){return h(S)}function L(){let e=o,a;return g(t=>{let n=A(t),r=null;return n&&(e&&(a=n),(e||a===n)&&(n=n.replace(/\.js$/,".lean.js")),r=P(()=>import(n),[])),o&&(e=!1),r},s.NotFound)}o&&D().then(({app:e,router:a,data:t})=>{a.go().then(()=>{p(a.route,t.site),e.mount("#app")})});export{D as createApp};
diff --git a/assets/chunks/framework.B63u0Dcf.js b/assets/chunks/framework.5XYse7Qj.js
similarity index 68%
rename from assets/chunks/framework.B63u0Dcf.js
rename to assets/chunks/framework.5XYse7Qj.js
index b664d20..dde1315 100644
--- a/assets/chunks/framework.B63u0Dcf.js
+++ b/assets/chunks/framework.5XYse7Qj.js
@@ -2,16 +2,16 @@
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diff --git a/assets/chunks/theme.DauYRQxa.js b/assets/chunks/theme.CECrkTxV.js
similarity index 80%
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To facilitate the use of deep mutational scanning for these important goals, we develop <a href=\\"https://dms-viz.github.io/\\" target=\\"_blank\\" rel=\\"noreferrer\\">interactive visualization tools</a> and <a href=\\"https://github.com/dms-vep/dms-vep-pipeline-3\\" target=\\"_blank\\" rel=\\"noreferrer\\">data analysis pipelines</a>. See <a href=\\"https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/\\" target=\\"_blank\\" rel=\\"noreferrer\\">here</a> for an example of how we analyze and visualize large datasets to inform the study of viral evolution.</p>\\n<h2 id=\\"interplay-of-immunity-and-viral-evolution\\" tabindex=\\"-1\\">Interplay of Immunity and Viral Evolution <a class=\\"header-anchor\\" href=\\"#interplay-of-immunity-and-viral-evolution\\" aria-label=\\"Permalink to &quot;Interplay of Immunity and Viral Evolution&quot;\\">&ZeroWidthSpace;</a></h2>\\n<p>We study immunity and viral evolution at both the population and single-cell levels.</p>\\n<p><img src=\\"/assets/research/seqneut.jpg\\" alt=\\"&quot;Sequencing-based neutralization assay&quot;\\"></p>\\n<p>At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both <a href=\\"https://www.sciencedirect.com/science/article/pii/S1931312824002336\\" target=\\"_blank\\" rel=\\"noreferrer\\">deep mutational scanning</a> and a <a href=\\"https://doi.org/10.1101/2024.03.08.584176\\" target=\\"_blank\\" rel=\\"noreferrer\\">sequencing based-neutralization assay</a> we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).</p>\\n<p>At the single-cell level, we developed approaches to <a href=\\"https://journals.asm.org/doi/10.1128/jvi.00500-19\\" target=\\"_blank\\" rel=\\"noreferrer\\">sequence viruses in single cells</a> and <a href=\\"https://elifesciences.org/articles/86852\\" target=\\"_blank\\" rel=\\"noreferrer\\">quantify how many progeny each infected cell produces</a>. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.</p>\\n<h2 id=\\"big-datasets-and-viral-evolution\\" tabindex=\\"-1\\">Big Datasets and Viral Evolution <a class=\\"header-anchor\\" href=\\"#big-datasets-and-viral-evolution\\" aria-label=\\"Permalink to &quot;Big Datasets and Viral Evolution&quot;\\">&ZeroWidthSpace;</a></h2>\\n<p>We also develop new ways to leverage large datasets to better understand viral evolution.</p>\\n<p>We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see <a href=\\"https://academic.oup.com/ve/article/9/2/vead055/7265011\\" target=\\"_blank\\" rel=\\"noreferrer\\">this paper</a> and <a href=\\"https://slides.com/jbloom/sars2-mut-fitness/\\" target=\\"_blank\\" rel=\\"noreferrer\\">these slides</a>). We've also created a platform to <a href=\\"https://jbloomlab.github.io/SARS2-mut-fitness/\\" target=\\"_blank\\" rel=\\"noreferrer\\">visualize the mutational effects</a> to aid in interpretation of viral evolution.</p>\\n<p>We have also integrated thousands of deep mutational scanning measurements into an <a href=\\"https://jbloomlab.github.io/SARS2-RBD-escape-calc/\\" target=\\"_blank\\" rel=\\"noreferrer\\">antibody-escape calculator</a> that was <a href=\\"https://slides.com/jbloom/sars2-rbd-escape-calc#/12\\" target=\\"_blank\\" rel=\\"noreferrer\\">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p>\\n<p>We also have projects that involve analyzing the evolution of viruses <a href=\\"https://elifesciences.org/articles/26875\\" target=\\"_blank\\" rel=\\"noreferrer\\">within individual infected humans</a>, and developing models to <a href=\\"https://academic.oup.com/ve/article/8/2/veac110/6889254\\" target=\\"_blank\\" rel=\\"noreferrer\\">understand epistasis among viral mutations</a>.</p>\\n"}]`),Go={data(){return{aims:eo,viruses:["Influenza","SARS-CoV-2","Lassa","Nipah","Rabies","HIV","Chikungunya","CoV-229E","Proteins"],currentVirus:"Viruses",virusIndex:-1,intervalId:null,colors:["#7F3C8D","#11A579","#3969AC","#F2B701","#E73F74","#80BA5A","#E68310","#008695","#CF1C90","#f97b72","#4b4b8f","#A5AA99"],useOpacity:!0,opacityLevel:.1,currentColor:"#000000"}},mounted(){this.intervalId=setInterval(this.updateVirus,4e3)},beforeDestroy(){clearInterval(this.intervalId)},methods:{updateVirus(){this.virusIndex=(this.virusIndex+1)%this.viruses.length,this.currentVirus=this.viruses[this.virusIndex],this.currentColor=this.colors[this.virusIndex]},getBackgroundWithOpacity(o){if(!this.useOpacity)return o;let e=o.match(/\w\w/g).map(t=>parseInt(t,16));return`rgba(${e[0]}, ${e[1]}, ${e[2]}, ${this.opacityLevel})`}},computed:{sortedAims(){return this.aims.sort((o,e)=>o.order-e.order)}}},to=o=>(Zt("data-v-ff69af82"),o=o(),Xt(),o),Uo={class:"mx-auto max-w-4xl px-4 text-left flex flex-col"},qo={class:"flex-grow"},Yo=to(()=>p("h1",{class:"text-4xl sm:text-5xl md:text-7xl lg:text-8xl text-gray-800 select-none"},[Q(" Welcome to the "),p("span",{class:"block font-bold"},"Bloom Lab")],-1)),Zo={class:"text-xl md:text-2xl lg:text-3xl text-gray-600 mt-2 lg:mt-4 select-none"},Xo=Qt('<p class="text-sm md:text-base lg:text-lg text-gray-500 mt-4 md:mt-6 lg:mt-12" data-v-ff69af82> In the <strong data-v-ff69af82>Bloom lab</strong>, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts. </p><p class="text-sm md:text-base lg:text-lg text-gray-500 mt-2 md:mt-4 lg:mt-6" data-v-ff69af82> Our lab is part of the <a href="https://www.fredhutch.org/en/research/divisions/basic-sciences-division.html" data-v-ff69af82>Basic Sciences Divison</a> and the <a href="https://www.fredhutch.org/en/research/divisions/public-health-sciences-division/research/computational-biology.html" data-v-ff69af82>Computational Biology Program</a> at the Fred Hutch. We are also affiliated with the <a href="https://www.gs.washington.edu/" data-v-ff69af82>Genome Sciences</a> and <a href="https://microbiology.washington.edu/uw-microbiology-home" data-v-ff69af82>Microbiology</a> Departments at the University of Washington, and graduate students often join our lab through the <a href="https://mcb-seattle.edu" data-v-ff69af82>MCB program</a>. Jesse Bloom is an Investigator of the <a href="https://www.hhmi.org/research" data-v-ff69af82>Howard Hughes Medical Institute</a>. </p>',2),Qo=to(()=>p("div",{class:"text-center mt-8 md:mt-12 mb-2"},[p("a",{href:"/research/",class:"no-underline text-gray-600 hover:text-gray-600 hover:shadow-md hover:shadow-custom-orange rounded-lg bg-custom-soft p-2 overflow-hidden transition-shadow duration-200 ease-in-out text-sm md:text-base lg:text-lg"},"Learn more about our research")],-1));function er(o,e,t,r,n,i){return h(),y("div",Uo,[p("div",qo,[Yo,p("p",Zo,[Q(" where we study the evolution of "),J(ht,{name:"fade",mode:"out-in"},{default:oe(()=>[(h(),y("span",{key:n.currentVirus,class:"italic",style:_o({color:n.currentColor,backgroundColor:i.getBackgroundWithOpacity(n.currentColor)})},j(n.currentVirus),5))]),_:1})]),Xo]),Qo])}const tr=K(Go,[["render",er],["__scopeId","data-v-ff69af82"]]),or={props:{date:String},methods:{getFormattedDate(){const o={year:"numeric",month:"long",day:"numeric"};return new Date(this.date).toLocaleDateString("en-US",o)}}},rr=p("dt",{class:"sr-only"},"Published on",-1),nr={class:"text-base leading-6 font-medium text-gray-500"},ir=["datetime"];function ar(o,e,t,r,n,i){return h(),y("dl",null,[rr,p("dd",nr,[p("time",{datetime:i.getFormattedDate()},j(i.getFormattedDate()),9,ir)])])}const sr=K(or,[["render",ar]]),lr=JSON.parse('[{"title":"Deep mutational scanning of H5 influenza hemagglutinin","author":"Jesse Bloom","date":"2024-05-25T00:00:00.000Z","excerpt":"<p>In <a href=\\"https://doi.org/10.1101/2024.05.23.595634\\" target=\\"_blank\\" rel=\\"noreferrer\\">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk.\\nThe data can be interactively visualized at <a href=\\"https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/\\" target=\\"_blank\\" rel=\\"noreferrer\\">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p>\\n","url":"/posts/h5-dms.html"},{"excerpt":"","url":"/posts/"}]'),cr={components:{Date:sr},data(){return{posts:lr.filter(o=>o.url.endsWith(".html")),frontmatter:fe().frontmatter}}},dr={class:"divide-y divide-gray-200"},ur=p("div",{class:"pt-6 pb-8 space-y-2 md:space-y-5"},[p("h1",{class:"text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14"}," Bloom Lab Blog "),p("p",{class:"text-lg leading-7 text-gray-600"}," A collection of thoughts, ideas, and projects from the Bloom Lab team. ")],-1),fr={class:"divide-y divide-gray-200"},pr={class:"space-y-2 xl:grid xl:grid-cols-4 xl:space-y-0 xl:items-baseline"},hr={class:"space-y-5 xl:col-span-3"},mr={class:"space-y-6"},gr={class:"text-2xl leading-8 font-bold tracking-tight"},br=["href"],vr=["innerHTML"],yr={class:"text-base leading-6 font-medium"},kr=["href"];function wr(o,e,t,r,n,i){const s=W("Date");return h(),y("div",dr,[ur,p("ul",fr,[(h(!0),y(H,null,Y(n.posts,a=>(h(),y("li",{class:"py-12",key:a.url},[p("article",pr,[J(s,{date:a.date},null,8,["date"]),p("div",hr,[p("div",mr,[p("h2",gr,[p("a",{class:"text-gray-900 hover:text-gray-900 no-underline",href:a.url},j(a.title),9,br)]),a.excerpt?(h(),y("div",{key:0,class:"max-w-none text-gray-500",innerHTML:a.excerpt},null,8,vr)):R("",!0)]),p("div",yr,[p("a",{class:"text-custom-orange no-underline","aria-label":"read more about {{ post.title }}",href:a.url},"Read more →",8,kr)])])])]))),128))])])}const xr=K(cr,[["render",wr]]),Sr=JSON.parse('[{"name":"Andrea Loes","image":"/assets/people/andrea-loes.jpg","title":"Staff Scientist/Lab Manager","category":"Staff","links":[{"link":"https://github.com/anloes","icon":"github"},{"link":"aloes@fredhutch.org","icon":"email"},{"link":"https://www.linkedin.com/in/andrea-loes-ph-d-59210419/","icon":"linkedin"}],"url":"/people/andrea-loes.html"},{"name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"},{"link":"https://andrewwbutler.com","icon":"website"}],"url":"/people/andrew-butler.html"},{"name":"Arjun Aditham","image":"/assets/people/arjun-aditham.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/arjunaditham","icon":"github"},{"link":"aaditham@fredhutch.org","icon":"email"},{"link":"https://www.linkedin.com/in/arjun-aditham/","icon":"linkedin"}],"url":"/people/arjun-aditham.html"},{"name":"Bernadeta Dadonaite","image":"/assets/people/bernadeta-dadonaite.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/Bernadetadad","icon":"github"},{"link":"https://x.com/bdadonaite?lang=en","icon":"twitter"},{"link":"bdadonai@fredhutch.org","icon":"email"}],"url":"/people/bernadeta-dadonaite.html"},{"name":"Brendan Larsen","image":"/assets/people/brendan-larsen.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/bblarsen-sci","icon":"github"},{"link":"https://x.com/bblarsen1","icon":"twitter"},{"link":"https://bblarsen-sci.github.io/about/","icon":"website"},{"link":"blarsen@fredhutch.org","icon":"email"}],"url":"/people/brendan-larsen.html"},{"name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}],"url":"/people/caelan-radford.html"},{"name":"Caleb Carr","image":"/assets/people/caleb-carr.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/Caleb-Carr","icon":"github"},{"link":"ccarr@fredhutch.org","icon":"email"}],"url":"/people/caleb-carr.html"},{"name":"Caroline 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To facilitate the use of deep mutational scanning for these important goals, we develop <a href=\\"https://dms-viz.github.io/\\" target=\\"_blank\\" rel=\\"noreferrer\\">interactive visualization tools</a> and <a href=\\"https://github.com/dms-vep/dms-vep-pipeline-3\\" target=\\"_blank\\" rel=\\"noreferrer\\">data analysis pipelines</a>. See <a href=\\"https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/\\" target=\\"_blank\\" rel=\\"noreferrer\\">here</a> for an example of how we analyze and visualize large datasets to inform the study of viral evolution.</p>\\n<h2 id=\\"interplay-of-immunity-and-viral-evolution\\" tabindex=\\"-1\\">Interplay of Immunity and Viral Evolution <a class=\\"header-anchor\\" href=\\"#interplay-of-immunity-and-viral-evolution\\" aria-label=\\"Permalink to &quot;Interplay of Immunity and Viral Evolution&quot;\\">&ZeroWidthSpace;</a></h2>\\n<p>We study immunity and viral evolution at both the population and single-cell levels.</p>\\n<p><img src=\\"/assets/research/seqneut.jpg\\" alt=\\"&quot;Sequencing-based neutralization assay&quot;\\"></p>\\n<p>At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both <a href=\\"https://www.sciencedirect.com/science/article/pii/S1931312824002336\\" target=\\"_blank\\" rel=\\"noreferrer\\">deep mutational scanning</a> and a <a href=\\"https://doi.org/10.1101/2024.03.08.584176\\" target=\\"_blank\\" rel=\\"noreferrer\\">sequencing based-neutralization assay</a> we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).</p>\\n<p>At the single-cell level, we developed approaches to <a href=\\"https://journals.asm.org/doi/10.1128/jvi.00500-19\\" target=\\"_blank\\" rel=\\"noreferrer\\">sequence viruses in single cells</a> and <a href=\\"https://elifesciences.org/articles/86852\\" target=\\"_blank\\" rel=\\"noreferrer\\">quantify how many progeny each infected cell produces</a>. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.</p>\\n<h2 id=\\"big-datasets-and-viral-evolution\\" tabindex=\\"-1\\">Big Datasets and Viral Evolution <a class=\\"header-anchor\\" href=\\"#big-datasets-and-viral-evolution\\" aria-label=\\"Permalink to &quot;Big Datasets and Viral Evolution&quot;\\">&ZeroWidthSpace;</a></h2>\\n<p>We also develop new ways to leverage large datasets to better understand viral evolution.</p>\\n<p>We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see <a href=\\"https://academic.oup.com/ve/article/9/2/vead055/7265011\\" target=\\"_blank\\" rel=\\"noreferrer\\">this paper</a> and <a href=\\"https://slides.com/jbloom/sars2-mut-fitness/\\" target=\\"_blank\\" rel=\\"noreferrer\\">these slides</a>). We've also created a platform to <a href=\\"https://jbloomlab.github.io/SARS2-mut-fitness/\\" target=\\"_blank\\" rel=\\"noreferrer\\">visualize the mutational effects</a> to aid in interpretation of viral evolution.</p>\\n<p>We have also integrated thousands of deep mutational scanning measurements into an <a href=\\"https://jbloomlab.github.io/SARS2-RBD-escape-calc/\\" target=\\"_blank\\" rel=\\"noreferrer\\">antibody-escape calculator</a> that was <a href=\\"https://slides.com/jbloom/sars2-rbd-escape-calc#/12\\" target=\\"_blank\\" rel=\\"noreferrer\\">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p>\\n<p>We also have projects that involve analyzing the evolution of viruses <a href=\\"https://elifesciences.org/articles/26875\\" target=\\"_blank\\" rel=\\"noreferrer\\">within individual infected humans</a>, and developing models to <a href=\\"https://academic.oup.com/ve/article/8/2/veac110/6889254\\" target=\\"_blank\\" rel=\\"noreferrer\\">understand epistasis among viral mutations</a>.</p>\\n"}]`),Go={data(){return{aims:eo,viruses:["Influenza","SARS-CoV-2","Lassa","Nipah","Rabies","HIV","Chikungunya","CoV-229E","Proteins"],currentVirus:"Viruses",virusIndex:-1,intervalId:null,colors:["#7F3C8D","#11A579","#3969AC","#F2B701","#E73F74","#80BA5A","#E68310","#008695","#CF1C90","#f97b72","#4b4b8f","#A5AA99"],useOpacity:!0,opacityLevel:.1,currentColor:"#000000"}},mounted(){this.intervalId=setInterval(this.updateVirus,4e3)},beforeDestroy(){clearInterval(this.intervalId)},methods:{updateVirus(){this.virusIndex=(this.virusIndex+1)%this.viruses.length,this.currentVirus=this.viruses[this.virusIndex],this.currentColor=this.colors[this.virusIndex]},getBackgroundWithOpacity(o){if(!this.useOpacity)return o;let e=o.match(/\w\w/g).map(t=>parseInt(t,16));return`rgba(${e[0]}, ${e[1]}, ${e[2]}, ${this.opacityLevel})`}},computed:{sortedAims(){return this.aims.sort((o,e)=>o.order-e.order)}}},to=o=>(Zt("data-v-ff69af82"),o=o(),Xt(),o),Uo={class:"mx-auto max-w-4xl px-4 text-left flex flex-col"},qo={class:"flex-grow"},Yo=to(()=>p("h1",{class:"text-4xl sm:text-5xl md:text-7xl lg:text-8xl text-gray-800 select-none"},[Q(" Welcome to the "),p("span",{class:"block font-bold"},"Bloom Lab")],-1)),Zo={class:"text-xl md:text-2xl lg:text-3xl text-gray-600 mt-2 lg:mt-4 select-none"},Xo=Qt('<p class="text-sm md:text-base lg:text-lg text-gray-500 mt-4 md:mt-6 lg:mt-12" data-v-ff69af82> In the <strong data-v-ff69af82>Bloom lab</strong>, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts. </p><p class="text-sm md:text-base lg:text-lg text-gray-500 mt-2 md:mt-4 lg:mt-6" data-v-ff69af82> Our lab is part of the <a href="https://www.fredhutch.org/en/research/divisions/basic-sciences-division.html" data-v-ff69af82>Basic Sciences Divison</a> and the <a href="https://www.fredhutch.org/en/research/divisions/public-health-sciences-division/research/computational-biology.html" data-v-ff69af82>Computational Biology Program</a> at the Fred Hutch. We are also affiliated with the <a href="https://www.gs.washington.edu/" data-v-ff69af82>Genome Sciences</a> and <a href="https://microbiology.washington.edu/uw-microbiology-home" data-v-ff69af82>Microbiology</a> Departments at the University of Washington, and graduate students often join our lab through the <a href="https://mcb-seattle.edu" data-v-ff69af82>MCB program</a>. 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index b1cba91..3ced3d3 100644
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similarity index 84%
rename from assets/index.md.D_bi7lf-.lean.js
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diff --git a/assets/papers_2013_ashenberg.md.B5rvuQTE.js b/assets/papers_2013_ashenberg.md.CMGBWYzK.js
similarity index 97%
rename from assets/papers_2013_ashenberg.md.B5rvuQTE.js
rename to assets/papers_2013_ashenberg.md.CMGBWYzK.js
index fe6acf3..eb43c46 100644
--- a/assets/papers_2013_ashenberg.md.B5rvuQTE.js
+++ b/assets/papers_2013_ashenberg.md.CMGBWYzK.js
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-import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const y=t(n,[["render",c]]);export{b as __pageData,y as default};
+import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const y=t(n,[["render",c]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2013_ashenberg.md.B5rvuQTE.lean.js b/assets/papers_2013_ashenberg.md.CMGBWYzK.lean.js
similarity index 97%
rename from assets/papers_2013_ashenberg.md.B5rvuQTE.lean.js
rename to assets/papers_2013_ashenberg.md.CMGBWYzK.lean.js
index fe6acf3..eb43c46 100644
--- a/assets/papers_2013_ashenberg.md.B5rvuQTE.lean.js
+++ b/assets/papers_2013_ashenberg.md.CMGBWYzK.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const y=t(n,[["render",c]]);export{b as __pageData,y as default};
+import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Mutational effects on stability are largely conserved during protein evolution","description":"","frontmatter":{"layout":"paper","title":"Mutational effects on stability are largely conserved during protein evolution","date":"2013-12-24","authors":["Orr Ashenberg","Lizhi Ian Gong","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1314781111","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1314781111","image":"/assets/papers/2013_ashenberg.jpg","keywords":["Epistasis","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2013_ashenberg.md","filePath":"papers/2013_ashenberg.md"}'),n={name:"papers/2013_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.",-1),l=[o,r];function c(h,d,p,u,f,g){return s(),a("div",null,l)}const y=t(n,[["render",c]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2013_gong.md.DsvuG6A0.js b/assets/papers_2013_gong.md.C_7YCWqG.js
similarity index 97%
rename from assets/papers_2013_gong.md.DsvuG6A0.js
rename to assets/papers_2013_gong.md.C_7YCWqG.js
index 510e2b5..9d9d754 100644
--- a/assets/papers_2013_gong.md.DsvuG6A0.js
+++ b/assets/papers_2013_gong.md.C_7YCWqG.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_gong.html"}]]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,h,u,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_gong.html"}]]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,h,u,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2013_gong.md.DsvuG6A0.lean.js b/assets/papers_2013_gong.md.C_7YCWqG.lean.js
similarity index 97%
rename from assets/papers_2013_gong.md.DsvuG6A0.lean.js
rename to assets/papers_2013_gong.md.C_7YCWqG.lean.js
index 510e2b5..9d9d754 100644
--- a/assets/papers_2013_gong.md.DsvuG6A0.lean.js
+++ b/assets/papers_2013_gong.md.C_7YCWqG.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_gong.html"}]]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,h,u,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Stability-mediated epistasis constrains the evolution of an influenza protein","description":"","frontmatter":{"layout":"paper","title":"Stability-mediated epistasis constrains the evolution of an influenza protein","date":"2013-05-14","authors":["Lizhi Ian Gong","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.7554/eLife.00631.001","link":"https://elifesciences.org/articles/631","image":"/assets/papers/2013_gong.jpg","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_gong.html"}]]},"headers":[],"relativePath":"papers/2013_gong.md","filePath":"papers/2013_gong.md"}'),n={name:"papers/2013_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.",-1),l=[s,r];function c(d,p,h,u,m,g){return i(),a("div",null,l)}const v=t(n,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2013_hooper.md.BwoShv7m.js b/assets/papers_2013_hooper.md.CtRDBRu8.js
similarity index 97%
rename from assets/papers_2013_hooper.md.BwoShv7m.js
rename to assets/papers_2013_hooper.md.CtRDBRu8.js
index 73c0bbb..06745ae 100644
--- a/assets/papers_2013_hooper.md.BwoShv7m.js
+++ b/assets/papers_2013_hooper.md.CtRDBRu8.js
@@ -1 +1 @@
-import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_hooper.html"}]]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,p,d,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default};
+import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_hooper.html"}]]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,p,d,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2013_hooper.md.BwoShv7m.lean.js b/assets/papers_2013_hooper.md.CtRDBRu8.lean.js
similarity index 97%
rename from assets/papers_2013_hooper.md.BwoShv7m.lean.js
rename to assets/papers_2013_hooper.md.CtRDBRu8.lean.js
index 73c0bbb..06745ae 100644
--- a/assets/papers_2013_hooper.md.BwoShv7m.lean.js
+++ b/assets/papers_2013_hooper.md.CtRDBRu8.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_hooper.html"}]]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,p,d,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default};
+import{_ as t,c as a,o as r,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","description":"","frontmatter":{"layout":"paper","title":"A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein","date":"2013-12-01","authors":["Kathryn A Hooper","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01889-13","link":"https://journals.asm.org/doi/full/10.1128/jvi.01889-13","image":"/assets/papers/2013_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2013_hooper.html"}]]},"headers":[],"relativePath":"papers/2013_hooper.md","filePath":"papers/2013_hooper.md"}'),n={name:"papers/2013_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.",-1),l=[o,s];function c(h,p,d,u,m,b){return r(),a("div",null,l)}const v=t(n,[["render",c]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2014_bloom_a.md.dR6xBFBy.js b/assets/papers_2014_bloom_a.md.eHGXDsBN.js
similarity index 95%
rename from assets/papers_2014_bloom_a.md.dR6xBFBy.js
rename to assets/papers_2014_bloom_a.md.eHGXDsBN.js
index ae3cf31..21337ce 100644
--- a/assets/papers_2014_bloom_a.md.dR6xBFBy.js
+++ b/assets/papers_2014_bloom_a.md.eHGXDsBN.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default};
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similarity index 95%
rename from assets/papers_2014_bloom_a.md.dR6xBFBy.lean.js
rename to assets/papers_2014_bloom_a.md.eHGXDsBN.lean.js
index ae3cf31..21337ce 100644
--- a/assets/papers_2014_bloom_a.md.dR6xBFBy.lean.js
+++ b/assets/papers_2014_bloom_a.md.eHGXDsBN.lean.js
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-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","description":"","frontmatter":{"layout":"paper","title":"An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs","date":"2014-10-01","authors":["Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msu220","link":"https://academic.oup.com/mbe/article/31/10/2753/1015257","image":"/assets/papers/2014_bloom_a.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_a.md","filePath":"papers/2014_bloom_a.md"}'),s={name:"papers/2014_bloom_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.",-1),l=[i,r];function m(c,h,d,p,u,g){return o(),a("div",null,l)}const y=t(s,[["render",m]]);export{b as __pageData,y as default};
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similarity index 93%
rename from assets/papers_2014_bloom_b.md.BUSsmnXP.js
rename to assets/papers_2014_bloom_b.md.CTHegYkT.js
index 321dc1e..97ca5ce 100644
--- a/assets/papers_2014_bloom_b.md.BUSsmnXP.js
+++ b/assets/papers_2014_bloom_b.md.CTHegYkT.js
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-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(c,d,p,h,u,g){return o(),a("div",null,l)}const f=t(r,[["render",m]]);export{b as __pageData,f as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(c,d,p,h,u,g){return o(),a("div",null,l)}const f=t(r,[["render",m]]);export{b as __pageData,f as default};
diff --git a/assets/papers_2014_bloom_b.md.BUSsmnXP.lean.js b/assets/papers_2014_bloom_b.md.CTHegYkT.lean.js
similarity index 93%
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rename to assets/papers_2014_bloom_b.md.CTHegYkT.lean.js
index 321dc1e..97ca5ce 100644
--- a/assets/papers_2014_bloom_b.md.BUSsmnXP.lean.js
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@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(c,d,p,h,u,g){return o(),a("div",null,l)}const f=t(r,[["render",m]]);export{b as __pageData,f as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","description":"","frontmatter":{"layout":"paper","title":"An experimentally determined evolutionary model dramatically improves phylogenetic fit","date":"2014-08-01","authors":["Jesse D Bloom"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msu173","link":"https://academic.oup.com/mbe/article/31/8/1956/2925795","image":"/assets/papers/2014_bloom_b.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2014_bloom_b.md","filePath":"papers/2014_bloom_b.md"}'),r={name:"papers/2014_bloom_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.",-1),l=[s,i];function m(c,d,p,h,u,g){return o(),a("div",null,l)}const f=t(r,[["render",m]]);export{b as __pageData,f as default};
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similarity index 97%
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rename to assets/papers_2014_gong.md.CCrM5t8e.js
index 7b2c4c9..2637923 100644
--- a/assets/papers_2014_gong.md.ZJ8fMGwf.js
+++ b/assets/papers_2014_gong.md.CCrM5t8e.js
@@ -1 +1 @@
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+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_gong.html"}]]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(c,u,d,h,f,m){return n(),a("div",null,l)}const _=t(o,[["render",p]]);export{y as __pageData,_ as default};
diff --git a/assets/papers_2014_gong.md.ZJ8fMGwf.lean.js b/assets/papers_2014_gong.md.CCrM5t8e.lean.js
similarity index 97%
rename from assets/papers_2014_gong.md.ZJ8fMGwf.lean.js
rename to assets/papers_2014_gong.md.CCrM5t8e.lean.js
index 7b2c4c9..2637923 100644
--- a/assets/papers_2014_gong.md.ZJ8fMGwf.lean.js
+++ b/assets/papers_2014_gong.md.CCrM5t8e.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_gong.html"}]]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(c,u,d,h,f,m){return n(),a("div",null,l)}const _=t(o,[["render",p]]);export{y as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","description":"","frontmatter":{"layout":"paper","title":"Epistatically interacting substitutions are enriched during adaptive protein evolution","date":"2014-05-08","authors":["Lizhi Ian Gong","Jesse D Bloom"],"journal":"PLoS genetics","doi":"10.1371/journal.pgen.1004328","link":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328","image":"/assets/papers/2014_gong.png","keywords":["Influenza","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_gong.html"}]]},"headers":[],"relativePath":"papers/2014_gong.md","filePath":"papers/2014_gong.md"}'),o={name:"papers/2014_gong.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.",-1),l=[s,r];function p(c,u,d,h,f,m){return n(),a("div",null,l)}const _=t(o,[["render",p]]);export{y as __pageData,_ as default};
diff --git a/assets/papers_2014_thyagarajan.md.EfyH60O5.js b/assets/papers_2014_thyagarajan.md.DLa3lyAU.js
similarity index 97%
rename from assets/papers_2014_thyagarajan.md.EfyH60O5.js
rename to assets/papers_2014_thyagarajan.md.DLa3lyAU.js
index fc0063f..f5ea134 100644
--- a/assets/papers_2014_thyagarajan.md.EfyH60O5.js
+++ b/assets/papers_2014_thyagarajan.md.DLa3lyAU.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_thyagarajan.html"}]]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),o={name:"papers/2014_thyagarajan.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[s,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(o,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_thyagarajan.html"}]]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),o={name:"papers/2014_thyagarajan.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[s,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(o,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2014_thyagarajan.md.EfyH60O5.lean.js b/assets/papers_2014_thyagarajan.md.DLa3lyAU.lean.js
similarity index 97%
rename from assets/papers_2014_thyagarajan.md.EfyH60O5.lean.js
rename to assets/papers_2014_thyagarajan.md.DLa3lyAU.lean.js
index fc0063f..f5ea134 100644
--- a/assets/papers_2014_thyagarajan.md.EfyH60O5.lean.js
+++ b/assets/papers_2014_thyagarajan.md.DLa3lyAU.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_thyagarajan.html"}]]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),o={name:"papers/2014_thyagarajan.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[s,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(o,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin","date":"2014-07-08","authors":["Bargavi Thyagarajan","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.03300","link":"https://elifesciences.org/articles/3300","image":"/assets/papers/2014_thyagarajan.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2014_thyagarajan.html"}]]},"headers":[],"relativePath":"papers/2014_thyagarajan.md","filePath":"papers/2014_thyagarajan.md"}'),o={name:"papers/2014_thyagarajan.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.",-1),c=[s,r];function l(h,u,g,d,f,m){return n(),a("div",null,c)}const b=t(o,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2015_bloom.md.BEpIVsNL.js b/assets/papers_2015_bloom.md.jT72heVp.js
similarity index 93%
rename from assets/papers_2015_bloom.md.BEpIVsNL.js
rename to assets/papers_2015_bloom.md.jT72heVp.js
index 2b77a83..ebdf7b1 100644
--- a/assets/papers_2015_bloom.md.BEpIVsNL.js
+++ b/assets/papers_2015_bloom.md.jT72heVp.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_bloom.html"}]]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,h,u,_){return o(),a("div",null,l)}const k=t(n,[["render",d]]);export{g as __pageData,k as default};
+import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_bloom.html"}]]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,h,u,_){return o(),a("div",null,l)}const k=t(n,[["render",d]]);export{g as __pageData,k as default};
diff --git a/assets/papers_2015_bloom.md.BEpIVsNL.lean.js b/assets/papers_2015_bloom.md.jT72heVp.lean.js
similarity index 93%
rename from assets/papers_2015_bloom.md.BEpIVsNL.lean.js
rename to assets/papers_2015_bloom.md.jT72heVp.lean.js
index 2b77a83..ebdf7b1 100644
--- a/assets/papers_2015_bloom.md.BEpIVsNL.lean.js
+++ b/assets/papers_2015_bloom.md.jT72heVp.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_bloom.html"}]]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,h,u,_){return o(),a("div",null,l)}const k=t(n,[["render",d]]);export{g as __pageData,k as default};
+import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Software for the analysis and visualization of deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"Software for the analysis and visualization of deep mutational scanning data","date":"2015-12-01","authors":["Jesse D Bloom"],"journal":"BMC bioinformatics","doi":"10.1186/s12859-015-0590-4","link":"https://link.springer.com/article/10.1186/s12859-015-0590-4","image":"/assets/papers/2015_bloom.jpg","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_bloom.html"}]]},"headers":[],"relativePath":"papers/2015_bloom.md","filePath":"papers/2015_bloom.md"}'),n={name:"papers/2015_bloom.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.",-1),c=e("p",null,"I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.",-1),l=[i,r,c];function d(m,p,f,h,u,_){return o(),a("div",null,l)}const k=t(n,[["render",d]]);export{g as __pageData,k as default};
diff --git a/assets/papers_2015_doud.md.C6K6MTxb.js b/assets/papers_2015_doud.md.ZKJOAoII.js
similarity index 97%
rename from assets/papers_2015_doud.md.C6K6MTxb.js
rename to assets/papers_2015_doud.md.ZKJOAoII.js
index 36e46ba..abcc2ff 100644
--- a/assets/papers_2015_doud.md.C6K6MTxb.js
+++ b/assets/papers_2015_doud.md.ZKJOAoII.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_doud.html"}]]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default};
+import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_doud.html"}]]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2015_doud.md.C6K6MTxb.lean.js b/assets/papers_2015_doud.md.ZKJOAoII.lean.js
similarity index 97%
rename from assets/papers_2015_doud.md.C6K6MTxb.lean.js
rename to assets/papers_2015_doud.md.ZKJOAoII.lean.js
index 36e46ba..abcc2ff 100644
--- a/assets/papers_2015_doud.md.C6K6MTxb.lean.js
+++ b/assets/papers_2015_doud.md.ZKJOAoII.lean.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_doud.html"}]]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default};
+import{_ as t,c as o,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","description":"","frontmatter":{"layout":"paper","title":"Site-specific amino acid preferences are mostly conserved in two closely related protein homologs","date":"2015-11-01","authors":["Michael B Doud","Orr Ashenberg","Jesse D Bloom"],"journal":"Molecular biology and evolution","doi":"10.1093/molbev/msv167","link":"https://academic.oup.com/mbe/article/32/11/2944/982113","image":"/assets/papers/2015_doud.jpg","keywords":["Influenza","Epistasis","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_doud.html"}]]},"headers":[],"relativePath":"papers/2015_doud.md","filePath":"papers/2015_doud.md"}'),a={name:"papers/2015_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.",-1),c=[s,r];function l(d,m,h,p,u,f){return i(),o("div",null,c)}const b=t(a,[["render",l]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2015_hooper.md.CyurnSiK.js b/assets/papers_2015_hooper.md.BSU8XgjD.js
similarity index 97%
rename from assets/papers_2015_hooper.md.CyurnSiK.js
rename to assets/papers_2015_hooper.md.BSU8XgjD.js
index b111ccf..275d07c 100644
--- a/assets/papers_2015_hooper.md.CyurnSiK.js
+++ b/assets/papers_2015_hooper.md.BSU8XgjD.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_hooper.html"}]]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),i={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(h,u,d,p,m,f){return n(),t("div",null,l)}const b=a(i,[["render",c]]);export{v as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_hooper.html"}]]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),i={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(h,u,d,p,m,f){return n(),t("div",null,l)}const b=a(i,[["render",c]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2015_hooper.md.CyurnSiK.lean.js b/assets/papers_2015_hooper.md.BSU8XgjD.lean.js
similarity index 97%
rename from assets/papers_2015_hooper.md.CyurnSiK.lean.js
rename to assets/papers_2015_hooper.md.BSU8XgjD.lean.js
index b111ccf..275d07c 100644
--- a/assets/papers_2015_hooper.md.CyurnSiK.lean.js
+++ b/assets/papers_2015_hooper.md.BSU8XgjD.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_hooper.html"}]]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),i={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(h,u,d,p,m,f){return n(),t("div",null,l)}const b=a(i,[["render",c]]);export{v as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","description":"","frontmatter":{"layout":"paper","title":"Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice","date":"2015-04-01","authors":["Kathryn A Hooper","James E Crowe Jr","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00012-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.00012-15","image":"/assets/papers/2015_hooper.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_hooper.html"}]]},"headers":[],"relativePath":"papers/2015_hooper.md","filePath":"papers/2015_hooper.md"}'),i={name:"papers/2015_hooper.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.",-1),l=[o,s];function c(h,u,d,p,m,f){return n(),t("div",null,l)}const b=a(i,[["render",c]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2015_machkovech.md.BFwFfcws.js b/assets/papers_2015_machkovech.md.DVMlkVR4.js
similarity index 97%
rename from assets/papers_2015_machkovech.md.BFwFfcws.js
rename to assets/papers_2015_machkovech.md.DVMlkVR4.js
index b2d4ae5..d1b6e4d 100644
--- a/assets/papers_2015_machkovech.md.BFwFfcws.js
+++ b/assets/papers_2015_machkovech.md.DVMlkVR4.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_machkovech.html"}]]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,p,u,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_machkovech.html"}]]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,p,u,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2015_machkovech.md.BFwFfcws.lean.js b/assets/papers_2015_machkovech.md.DVMlkVR4.lean.js
similarity index 97%
rename from assets/papers_2015_machkovech.md.BFwFfcws.lean.js
rename to assets/papers_2015_machkovech.md.DVMlkVR4.lean.js
index b2d4ae5..d1b6e4d 100644
--- a/assets/papers_2015_machkovech.md.BFwFfcws.lean.js
+++ b/assets/papers_2015_machkovech.md.DVMlkVR4.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_machkovech.html"}]]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,p,u,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","description":"","frontmatter":{"layout":"paper","title":"Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages","date":"2015-11-15","authors":["Heather M Machkovech","Trevor Bedford","Marc A Suchard","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.01571-15","link":"https://journals.asm.org/doi/full/10.1128/jvi.01571-15","image":"/assets/papers/2015_machkovech.jpg","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2015_machkovech.html"}]]},"headers":[],"relativePath":"papers/2015_machkovech.md","filePath":"papers/2015_machkovech.md"}'),s={name:"papers/2015_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.",-1),l=[o,r];function c(h,p,u,d,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2016_doud.md.deIqup8A.js b/assets/papers_2016_doud.md.C4wflz3g.js
similarity index 94%
rename from assets/papers_2016_doud.md.deIqup8A.js
rename to assets/papers_2016_doud.md.C4wflz3g.js
index 11bde72..2620a91 100644
--- a/assets/papers_2016_doud.md.deIqup8A.js
+++ b/assets/papers_2016_doud.md.C4wflz3g.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_doud.html"}]]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const v=t(i,[["render",u]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_doud.html"}]]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const v=t(i,[["render",u]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2016_doud.md.deIqup8A.lean.js b/assets/papers_2016_doud.md.C4wflz3g.lean.js
similarity index 94%
rename from assets/papers_2016_doud.md.deIqup8A.lean.js
rename to assets/papers_2016_doud.md.C4wflz3g.lean.js
index 11bde72..2620a91 100644
--- a/assets/papers_2016_doud.md.deIqup8A.lean.js
+++ b/assets/papers_2016_doud.md.C4wflz3g.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_doud.html"}]]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const v=t(i,[["render",u]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin","date":"2016-06-03","authors":["Michael B Doud","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v8060155","link":"https://www.mdpi.com/1999-4915/8/6/155","image":"/assets/papers/2016_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_doud.html"}]]},"headers":[],"relativePath":"papers/2016_doud.md","filePath":"papers/2016_doud.md"}'),i={name:"papers/2016_doud.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.",-1),l=[s,r];function u(c,m,h,d,f,p){return o(),a("div",null,l)}const v=t(i,[["render",u]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2016_haddox.md.C7vDgGwS.js b/assets/papers_2016_haddox.md.uyoqYhk0.js
similarity index 97%
rename from assets/papers_2016_haddox.md.C7vDgGwS.js
rename to assets/papers_2016_haddox.md.uyoqYhk0.js
index f596f0b..1c54c44 100644
--- a/assets/papers_2016_haddox.md.C7vDgGwS.js
+++ b/assets/papers_2016_haddox.md.uyoqYhk0.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_haddox.html"}]]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_haddox.html"}]]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default};
diff --git a/assets/papers_2016_haddox.md.C7vDgGwS.lean.js b/assets/papers_2016_haddox.md.uyoqYhk0.lean.js
similarity index 97%
rename from assets/papers_2016_haddox.md.C7vDgGwS.lean.js
rename to assets/papers_2016_haddox.md.uyoqYhk0.lean.js
index f596f0b..1c54c44 100644
--- a/assets/papers_2016_haddox.md.C7vDgGwS.lean.js
+++ b/assets/papers_2016_haddox.md.uyoqYhk0.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_haddox.html"}]]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","description":"","frontmatter":{"layout":"paper","title":"Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture","date":"2016-12-13","authors":["Hugh K Haddox","Adam S Dingens","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006114","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114","image":"/assets/papers/2016_haddox.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_haddox.html"}]]},"headers":[],"relativePath":"papers/2016_haddox.md","filePath":"papers/2016_haddox.md"}'),i={name:"papers/2016_haddox.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.",-1),l=[s,r];function c(u,d,p,h,m,f){return n(),a("div",null,l)}const _=t(i,[["render",c]]);export{v as __pageData,_ as default};
diff --git a/assets/papers_2016_xue.md.CLOKSIVX.js b/assets/papers_2016_xue.md.0j6fekiL.js
similarity index 97%
rename from assets/papers_2016_xue.md.CLOKSIVX.js
rename to assets/papers_2016_xue.md.0j6fekiL.js
index d088906..6317244 100644
--- a/assets/papers_2016_xue.md.CLOKSIVX.js
+++ b/assets/papers_2016_xue.md.0j6fekiL.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_xue.html"}]]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,m,f){return i(),a("div",null,l)}const b=t(o,[["render",c]]);export{_ as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_xue.html"}]]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,m,f){return i(),a("div",null,l)}const b=t(o,[["render",c]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2016_xue.md.CLOKSIVX.lean.js b/assets/papers_2016_xue.md.0j6fekiL.lean.js
similarity index 97%
rename from assets/papers_2016_xue.md.CLOKSIVX.lean.js
rename to assets/papers_2016_xue.md.0j6fekiL.lean.js
index d088906..6317244 100644
--- a/assets/papers_2016_xue.md.CLOKSIVX.lean.js
+++ b/assets/papers_2016_xue.md.0j6fekiL.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_xue.html"}]]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,m,f){return i(),a("div",null,l)}const b=t(o,[["render",c]]);export{_ as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","description":"","frontmatter":{"layout":"paper","title":"Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture","date":"2016-03-15","authors":["Katherine S Xue","Kathryn A Hooper","Anja R Ollodart","Adam S Dingens","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.13974.001","link":"https://elifesciences.org/articles/13974","image":"/assets/papers/2016_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2016_xue.html"}]]},"headers":[],"relativePath":"papers/2016_xue.md","filePath":"papers/2016_xue.md"}'),o={name:"papers/2016_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.",-1),l=[s,r];function c(p,d,u,h,m,f){return i(),a("div",null,l)}const b=t(o,[["render",c]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2017_ashenberg.md.CJzyhso1.js b/assets/papers_2017_ashenberg.md.CqAqjCx-.js
similarity index 97%
rename from assets/papers_2017_ashenberg.md.CJzyhso1.js
rename to assets/papers_2017_ashenberg.md.CqAqjCx-.js
index 931952f..371334e 100644
--- a/assets/papers_2017_ashenberg.md.CJzyhso1.js
+++ b/assets/papers_2017_ashenberg.md.CqAqjCx-.js
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-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,p,d,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,p,d,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2017_ashenberg.md.CJzyhso1.lean.js b/assets/papers_2017_ashenberg.md.CqAqjCx-.lean.js
similarity index 97%
rename from assets/papers_2017_ashenberg.md.CJzyhso1.lean.js
rename to assets/papers_2017_ashenberg.md.CqAqjCx-.lean.js
index 931952f..371334e 100644
--- a/assets/papers_2017_ashenberg.md.CJzyhso1.lean.js
+++ b/assets/papers_2017_ashenberg.md.CqAqjCx-.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,p,d,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA","date":"2017-03-27","authors":["Orr Ashenberg","Jai Padmakumar","Michael B Doud","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1006288","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288","image":"/assets/papers/2017_ashenberg.png","keywords":["Deep mutational scanning","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_ashenberg.html"}]]},"headers":[],"relativePath":"papers/2017_ashenberg.md","filePath":"papers/2017_ashenberg.md"}'),s={name:"papers/2017_ashenberg.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.",-1),l=[o,r];function c(h,f,u,p,d,m){return i(),a("div",null,l)}const v=t(s,[["render",c]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2017_bloom.md.DOjgXCgU.js b/assets/papers_2017_bloom.md.CTVjkGQE.js
similarity index 95%
rename from assets/papers_2017_bloom.md.DOjgXCgU.js
rename to assets/papers_2017_bloom.md.CTVjkGQE.js
index ac0e720..e68766c 100644
--- a/assets/papers_2017_bloom.md.DOjgXCgU.js
+++ b/assets/papers_2017_bloom.md.CTVjkGQE.js
@@ -1 +1 @@
-import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_bloom.html"}]]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,h,_){return s(),o("div",null,l)}const g=t(a,[["render",c]]);export{b as __pageData,g as default};
+import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_bloom.html"}]]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,h,_){return s(),o("div",null,l)}const g=t(a,[["render",c]]);export{b as __pageData,g as default};
diff --git a/assets/papers_2017_bloom.md.DOjgXCgU.lean.js b/assets/papers_2017_bloom.md.CTVjkGQE.lean.js
similarity index 95%
rename from assets/papers_2017_bloom.md.DOjgXCgU.lean.js
rename to assets/papers_2017_bloom.md.CTVjkGQE.lean.js
index ac0e720..e68766c 100644
--- a/assets/papers_2017_bloom.md.DOjgXCgU.lean.js
+++ b/assets/papers_2017_bloom.md.CTVjkGQE.lean.js
@@ -1 +1 @@
-import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_bloom.html"}]]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,h,_){return s(),o("div",null,l)}const g=t(a,[["render",c]]);export{b as __pageData,g as default};
+import{_ as t,c as o,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","description":"","frontmatter":{"layout":"paper","title":"Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models","date":"2017-12-01","authors":["Jesse D Bloom"],"journal":"Biology direct","doi":"10.1186/s13062-016-0172-z","link":"https://link.springer.com/article/10.1186/s13062-016-0172-z","image":"/assets/papers/2017_bloom.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_bloom.html"}]]},"headers":[],"relativePath":"papers/2017_bloom.md","filePath":"papers/2017_bloom.md"}'),a={name:"papers/2017_bloom.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.",-1),l=[n,r];function c(d,m,p,f,h,_){return s(),o("div",null,l)}const g=t(a,[["render",c]]);export{b as __pageData,g as default};
diff --git a/assets/papers_2017_dingens.md.CEcqttnv.js b/assets/papers_2017_dingens.md.BR2hL2tL.js
similarity index 97%
rename from assets/papers_2017_dingens.md.CEcqttnv.js
rename to assets/papers_2017_dingens.md.BR2hL2tL.js
index f709bd2..cfe0c43 100644
--- a/assets/papers_2017_dingens.md.CEcqttnv.js
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--- a/assets/papers_2017_xue.md.CVF3vCqo.js
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@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_xue.html"}]]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),o={name:"papers/2017_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[s,l];function c(p,u,d,h,m,f){return n(),a("div",null,r)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_xue.html"}]]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),o={name:"papers/2017_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[s,l];function c(p,u,d,h,m,f){return n(),a("div",null,r)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2017_xue.md.CVF3vCqo.lean.js b/assets/papers_2017_xue.md.BCSmjYyI.lean.js
similarity index 97%
rename from assets/papers_2017_xue.md.CVF3vCqo.lean.js
rename to assets/papers_2017_xue.md.BCSmjYyI.lean.js
index 9aec1ee..553a184 100644
--- a/assets/papers_2017_xue.md.CVF3vCqo.lean.js
+++ b/assets/papers_2017_xue.md.BCSmjYyI.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_xue.html"}]]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),o={name:"papers/2017_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[s,l];function c(p,u,d,h,m,f){return n(),a("div",null,r)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Parallel evolution of influenza across multiple spatiotemporal scales","description":"","frontmatter":{"layout":"paper","title":"Parallel evolution of influenza across multiple spatiotemporal scales","date":"2017-06-27","authors":["Katherine S Xue","Terry Stevens-Ayers","Angela P Campbell","Janet A Englund","Steven A Pergam","Michael Boeckh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.26875.001","link":"https://elifesciences.org/articles/26875","image":"/assets/papers/2017_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2017_xue.html"}]]},"headers":[],"relativePath":"papers/2017_xue.md","filePath":"papers/2017_xue.md"}'),o={name:"papers/2017_xue.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,"Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.",-1),r=[s,l];function c(p,u,d,h,m,f){return n(),a("div",null,r)}const v=t(o,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2018_dingens.md.B2Iid0QZ.js b/assets/papers_2018_dingens.md.CtJ7fU0n.js
similarity index 97%
rename from assets/papers_2018_dingens.md.B2Iid0QZ.js
rename to assets/papers_2018_dingens.md.CtJ7fU0n.js
index 41183a4..53ca502 100644
--- a/assets/papers_2018_dingens.md.B2Iid0QZ.js
+++ b/assets/papers_2018_dingens.md.CtJ7fU0n.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_dingens.html"}]]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,h,u,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_dingens.html"}]]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,h,u,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2018_dingens.md.B2Iid0QZ.lean.js b/assets/papers_2018_dingens.md.CtJ7fU0n.lean.js
similarity index 97%
rename from assets/papers_2018_dingens.md.B2Iid0QZ.lean.js
rename to assets/papers_2018_dingens.md.CtJ7fU0n.lean.js
index 41183a4..53ca502 100644
--- a/assets/papers_2018_dingens.md.B2Iid0QZ.lean.js
+++ b/assets/papers_2018_dingens.md.CtJ7fU0n.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_dingens.html"}]]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,h,u,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","description":"","frontmatter":{"layout":"paper","title":"Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV","date":"2018-07-05","authors":["Adam S Dingens","Priyamvada Acharya","Hugh K Haddox","Reda Rawi","Kai Xu","Gwo-Yu Chuang","Hui Wei","Baoshan Zhang","John R Mascola","Bridget Carragher","Clinton S Potter","Julie Overbaugh","Peter D Kwong","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007159","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159","image":"/assets/papers/2018_dingens.png","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_dingens.html"}]]},"headers":[],"relativePath":"papers/2018_dingens.md","filePath":"papers/2018_dingens.md"}'),o={name:"papers/2018_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.",-1),c=[s,r];function d(p,l,h,u,f,m){return i(),a("div",null,c)}const v=t(o,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2018_doud.md.0WEMa0My.js b/assets/papers_2018_doud.md.DWEV2o7B.js
similarity index 97%
rename from assets/papers_2018_doud.md.0WEMa0My.js
rename to assets/papers_2018_doud.md.DWEV2o7B.js
index 2ba570d..48a30ef 100644
--- a/assets/papers_2018_doud.md.0WEMa0My.js
+++ b/assets/papers_2018_doud.md.DWEV2o7B.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_doud.html"}]]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function d(c,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",d]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_doud.html"}]]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function d(c,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",d]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2018_doud.md.0WEMa0My.lean.js b/assets/papers_2018_doud.md.DWEV2o7B.lean.js
similarity index 97%
rename from assets/papers_2018_doud.md.0WEMa0My.lean.js
rename to assets/papers_2018_doud.md.DWEV2o7B.lean.js
index 2ba570d..48a30ef 100644
--- a/assets/papers_2018_doud.md.0WEMa0My.lean.js
+++ b/assets/papers_2018_doud.md.DWEV2o7B.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_doud.html"}]]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function d(c,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",d]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin","date":"2018-04-11","authors":["Michael B Doud*","Juhye M Lee*","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-018-03665-3","link":"https://www.nature.com/articles/s41467-018-03665-3","image":"/assets/papers/2018_doud.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_doud.html"}]]},"headers":[],"relativePath":"papers/2018_doud.md","filePath":"papers/2018_doud.md"}'),n={name:"papers/2018_doud.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.",-1),l=[o,r];function d(c,u,h,m,p,f){return i(),t("div",null,l)}const _=a(n,[["render",d]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2018_haddox.md.ChmWZLIP.js b/assets/papers_2018_haddox.md.YxraawCs.js
similarity index 97%
rename from assets/papers_2018_haddox.md.ChmWZLIP.js
rename to assets/papers_2018_haddox.md.YxraawCs.js
index 1a20be8..9f06623 100644
--- a/assets/papers_2018_haddox.md.ChmWZLIP.js
+++ b/assets/papers_2018_haddox.md.YxraawCs.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_haddox.html"}]]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),i={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),t("div",null,l)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
+import{_ as a,c as t,o as s,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_haddox.html"}]]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),i={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),t("div",null,l)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2018_haddox.md.ChmWZLIP.lean.js b/assets/papers_2018_haddox.md.YxraawCs.lean.js
similarity index 97%
rename from assets/papers_2018_haddox.md.ChmWZLIP.lean.js
rename to assets/papers_2018_haddox.md.YxraawCs.lean.js
index 1a20be8..9f06623 100644
--- a/assets/papers_2018_haddox.md.ChmWZLIP.lean.js
+++ b/assets/papers_2018_haddox.md.YxraawCs.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_haddox.html"}]]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),i={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),t("div",null,l)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
+import{_ as a,c as t,o as s,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","description":"","frontmatter":{"layout":"paper","title":"Mapping mutational effects along the evolutionary landscape of HIV envelope","date":"2018-03-28","authors":["Hugh K Haddox*","Adam S Dingens*","Sarah K Hilton","Julie Overbaugh","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.34420","link":"https://elifesciences.org/articles/34420","image":"/assets/papers/2018_haddox.jpg","keywords":["HIV","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_haddox.html"}]]},"headers":[],"relativePath":"papers/2018_haddox.md","filePath":"papers/2018_haddox.md"}'),i={name:"papers/2018_haddox.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at > 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.",-1),l=[n,r];function c(d,h,f,p,u,m){return s(),t("div",null,l)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2018_hilton.md.BHv73fUD.js b/assets/papers_2018_hilton.md.BBzQyyE5.js
similarity index 97%
rename from assets/papers_2018_hilton.md.BHv73fUD.js
rename to assets/papers_2018_hilton.md.BBzQyyE5.js
index cbd9cef..5ba6867 100644
--- a/assets/papers_2018_hilton.md.BHv73fUD.js
+++ b/assets/papers_2018_hilton.md.BBzQyyE5.js
@@ -1 +1 @@
-import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_hilton.html"}]]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(h,d,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default};
+import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_hilton.html"}]]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(h,d,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default};
diff --git a/assets/papers_2018_hilton.md.BHv73fUD.lean.js b/assets/papers_2018_hilton.md.BBzQyyE5.lean.js
similarity index 97%
rename from assets/papers_2018_hilton.md.BHv73fUD.lean.js
rename to assets/papers_2018_hilton.md.BBzQyyE5.lean.js
index cbd9cef..5ba6867 100644
--- a/assets/papers_2018_hilton.md.BHv73fUD.lean.js
+++ b/assets/papers_2018_hilton.md.BBzQyyE5.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_hilton.html"}]]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(h,d,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default};
+import{_ as t,c as i,o as s,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","description":"","frontmatter":{"layout":"paper","title":"Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence","date":"2018-07-01","authors":["Sarah K Hilton","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/vey033","link":"https://academic.oup.com/ve/article/4/2/vey033/5163287","image":"/assets/papers/2018_hilton.jpg","keywords":["Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_hilton.html"}]]},"headers":[],"relativePath":"papers/2018_hilton.md","filePath":"papers/2018_hilton.md"}'),a={name:"papers/2018_hilton.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.",-1),c=[o,r];function l(h,d,m,p,f,u){return s(),i("div",null,c)}const y=t(a,[["render",l]]);export{v as __pageData,y as default};
diff --git a/assets/papers_2018_lee.md.BISXlPRD.js b/assets/papers_2018_lee.md.F5x56T3l.js
similarity index 97%
rename from assets/papers_2018_lee.md.BISXlPRD.js
rename to assets/papers_2018_lee.md.F5x56T3l.js
index d909150..dfebbf9 100644
--- a/assets/papers_2018_lee.md.BISXlPRD.js
+++ b/assets/papers_2018_lee.md.F5x56T3l.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_lee.html"}]]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,h,m,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_lee.html"}]]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,h,m,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default};
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--- a/assets/papers_2018_lee.md.BISXlPRD.lean.js
+++ b/assets/papers_2018_lee.md.F5x56T3l.lean.js
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-import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_lee.html"}]]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,h,m,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as n,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants","date":"2018-08-28","authors":["Juhye M Lee","John Huddleston","Michael B Doud","Kathryn A Hooper","Nicholas C Wu","Trevor Bedford","Jesse D Bloom"],"journal":"PNAS","doi":"10.1073/pnas.1806133115","link":"https://www.pnas.org/doi/abs/10.1073/pnas.1806133115","image":"/assets/papers/2018_lee.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_lee.html"}]]},"headers":[],"relativePath":"papers/2018_lee.md","filePath":"papers/2018_lee.md"}'),r={name:"papers/2018_lee.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.",-1),l=[i,o];function u(c,d,h,m,f,p){return n(),t("div",null,l)}const _=a(r,[["render",u]]);export{g as __pageData,_ as default};
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similarity index 96%
rename from assets/papers_2018_russell.md.YvWiIb1q.js
rename to assets/papers_2018_russell.md.ChQsaRHY.js
index 97b4604..168e286 100644
--- a/assets/papers_2018_russell.md.YvWiIb1q.js
+++ b/assets/papers_2018_russell.md.ChQsaRHY.js
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-import{_ as a,c as t,o as l,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_russell.html"}]]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),i={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(p,u,f,m,d,h){return l(),t("div",null,o)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
+import{_ as a,c as t,o as l,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_russell.html"}]]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),i={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(p,u,f,m,d,h){return l(),t("div",null,o)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2018_russell.md.YvWiIb1q.lean.js b/assets/papers_2018_russell.md.ChQsaRHY.lean.js
similarity index 96%
rename from assets/papers_2018_russell.md.YvWiIb1q.lean.js
rename to assets/papers_2018_russell.md.ChQsaRHY.lean.js
index 97b4604..168e286 100644
--- a/assets/papers_2018_russell.md.YvWiIb1q.lean.js
+++ b/assets/papers_2018_russell.md.ChQsaRHY.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as l,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_russell.html"}]]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),i={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(p,u,f,m,d,h){return l(),t("div",null,o)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
+import{_ as a,c as t,o as l,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Extreme heterogeneity of influenza virus infection in single cells","description":"","frontmatter":{"layout":"paper","title":"Extreme heterogeneity of influenza virus infection in single cells","date":"2018-02-16","authors":["Alistair B Russell","Cole Trapnell","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.32303","link":"https://elifesciences.org/articles/32303","image":"/assets/papers/2018_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_russell.html"}]]},"headers":[],"relativePath":"papers/2018_russell.md","filePath":"papers/2018_russell.md"}'),i={name:"papers/2018_russell.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.",-1),o=[n,r];function c(p,u,f,m,d,h){return l(),t("div",null,o)}const g=a(i,[["render",c]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2018_xue_a.md.4IbmgWUZ.js b/assets/papers_2018_xue_a.md.BsbzmimN.js
similarity index 96%
rename from assets/papers_2018_xue_a.md.4IbmgWUZ.js
rename to assets/papers_2018_xue_a.md.BsbzmimN.js
index b676832..450de48 100644
--- a/assets/papers_2018_xue_a.md.4IbmgWUZ.js
+++ b/assets/papers_2018_xue_a.md.BsbzmimN.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_a.html"}]]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),o={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return a(),i("div",null,l)}const b=t(o,[["render",u]]);export{v as __pageData,b as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_a.html"}]]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),o={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return a(),i("div",null,l)}const b=t(o,[["render",u]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2018_xue_a.md.4IbmgWUZ.lean.js b/assets/papers_2018_xue_a.md.BsbzmimN.lean.js
similarity index 96%
rename from assets/papers_2018_xue_a.md.4IbmgWUZ.lean.js
rename to assets/papers_2018_xue_a.md.BsbzmimN.lean.js
index b676832..450de48 100644
--- a/assets/papers_2018_xue_a.md.4IbmgWUZ.lean.js
+++ b/assets/papers_2018_xue_a.md.BsbzmimN.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_a.html"}]]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),o={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return a(),i("div",null,l)}const b=t(o,[["render",u]]);export{v as __pageData,b as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Within-host evolution of human influenza virus","description":"","frontmatter":{"layout":"paper","title":"Within-host evolution of human influenza virus","date":"2018-09-01","authors":["Katherine S Xue","Louise H Moncla","Trevor Bedford","Jesse D Bloom"],"journal":"Trends in Microbiology","doi":"10.1016/j.tim.2018.02.007","link":"https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X","image":"/assets/papers/2018_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_a.html"}]]},"headers":[],"relativePath":"papers/2018_xue_a.md","filePath":"papers/2018_xue_a.md"}'),o={name:"papers/2018_xue_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.",-1),l=[s,r];function u(c,h,d,p,f,_){return a(),i("div",null,l)}const b=t(o,[["render",u]]);export{v as __pageData,b as default};
diff --git a/assets/papers_2018_xue_b.md.fJsqLb44.js b/assets/papers_2018_xue_b.md.5P6jAK9a.js
similarity index 97%
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rename to assets/papers_2018_xue_b.md.5P6jAK9a.js
index cbcdb91..0d993dd 100644
--- a/assets/papers_2018_xue_b.md.fJsqLb44.js
+++ b/assets/papers_2018_xue_b.md.5P6jAK9a.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_b.html"}]]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,p,d,h,f,m){return i(),t("div",null,l)}const v=a(r,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_b.html"}]]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,p,d,h,f,m){return i(),t("div",null,l)}const v=a(r,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2018_xue_b.md.fJsqLb44.lean.js b/assets/papers_2018_xue_b.md.5P6jAK9a.lean.js
similarity index 97%
rename from assets/papers_2018_xue_b.md.fJsqLb44.lean.js
rename to assets/papers_2018_xue_b.md.5P6jAK9a.lean.js
index cbcdb91..0d993dd 100644
--- a/assets/papers_2018_xue_b.md.fJsqLb44.lean.js
+++ b/assets/papers_2018_xue_b.md.5P6jAK9a.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_b.html"}]]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,p,d,h,f,m){return i(),t("div",null,l)}const v=a(r,[["render",c]]);export{_ as __pageData,v as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","description":"","frontmatter":{"layout":"paper","title":"Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples","date":"2018-02-28","authors":["Katherine S Xue","Alexander L Greninger","Ailyn Pérez-Osorio","Jesse D Bloom"],"journal":"MSphere","doi":"10.1128/mspheredirect.00552-17","link":"https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17","image":"/assets/papers/2018_xue_b.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2018_xue_b.html"}]]},"headers":[],"relativePath":"papers/2018_xue_b.md","filePath":"papers/2018_xue_b.md"}'),r={name:"papers/2018_xue_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.",-1),l=[s,o];function c(u,p,d,h,f,m){return i(),t("div",null,l)}const v=a(r,[["render",c]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2019_crawford.md.DgY5Di-h.js b/assets/papers_2019_crawford.md.BleYLE1S.js
similarity index 97%
rename from assets/papers_2019_crawford.md.DgY5Di-h.js
rename to assets/papers_2019_crawford.md.BleYLE1S.js
index 1af7266..478763d 100644
--- a/assets/papers_2019_crawford.md.DgY5Di-h.js
+++ b/assets/papers_2019_crawford.md.BleYLE1S.js
@@ -1 +1 @@
-import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_crawford.html"}]]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),o={name:"papers/2019_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[n,i];function l(u,h,d,p,f,g){return t(),s("div",null,c)}const b=a(o,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_crawford.html"}]]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),o={name:"papers/2019_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[n,i];function l(u,h,d,p,f,g){return t(),s("div",null,c)}const b=a(o,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2019_crawford.md.DgY5Di-h.lean.js b/assets/papers_2019_crawford.md.BleYLE1S.lean.js
similarity index 97%
rename from assets/papers_2019_crawford.md.DgY5Di-h.lean.js
rename to assets/papers_2019_crawford.md.BleYLE1S.lean.js
index 1af7266..478763d 100644
--- a/assets/papers_2019_crawford.md.DgY5Di-h.lean.js
+++ b/assets/papers_2019_crawford.md.BleYLE1S.lean.js
@@ -1 +1 @@
-import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_crawford.html"}]]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),o={name:"papers/2019_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[n,i];function l(u,h,d,p,f,g){return t(),s("div",null,c)}const b=a(o,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","description":"","frontmatter":{"layout":"paper","title":"alignparse: A Python package for parsing complex features from high-throughput long-read sequencing","date":"2019-01-23","authors":["Katharine HD Crawford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.01915","link":"https://doi.org/10.21105%2Fjoss.01915","image":"/assets/papers/2019_crawford.png","keywords":["Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_crawford.html"}]]},"headers":[],"relativePath":"papers/2019_crawford.md","filePath":"papers/2019_crawford.md"}'),o={name:"papers/2019_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads & Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson & Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.",-1),c=[n,i];function l(u,h,d,p,f,g){return t(),s("div",null,c)}const b=a(o,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2019_dingens_a.md.D4ylMh50.js b/assets/papers_2019_dingens_a.md.CBcjQWpL.js
similarity index 97%
rename from assets/papers_2019_dingens_a.md.D4ylMh50.js
rename to assets/papers_2019_dingens_a.md.CBcjQWpL.js
index 76c5fe2..abe4b25 100644
--- a/assets/papers_2019_dingens_a.md.D4ylMh50.js
+++ b/assets/papers_2019_dingens_a.md.CBcjQWpL.js
@@ -1 +1 @@
-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_a.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,h,u,p,f,m){return n(),i("div",null,d)}const v=t(s,[["render",l]]);export{_ as __pageData,v as default};
+import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_a.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,h,u,p,f,m){return n(),i("div",null,d)}const v=t(s,[["render",l]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2019_dingens_a.md.D4ylMh50.lean.js b/assets/papers_2019_dingens_a.md.CBcjQWpL.lean.js
similarity index 97%
rename from assets/papers_2019_dingens_a.md.D4ylMh50.lean.js
rename to assets/papers_2019_dingens_a.md.CBcjQWpL.lean.js
index 76c5fe2..abe4b25 100644
--- a/assets/papers_2019_dingens_a.md.D4ylMh50.lean.js
+++ b/assets/papers_2019_dingens_a.md.CBcjQWpL.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_a.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,h,u,p,f,m){return n(),i("div",null,d)}const v=t(s,[["render",l]]);export{_ as __pageData,v as default};
+import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","description":"","frontmatter":{"layout":"paper","title":"Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide","date":"2019-05-15","authors":["Adam S Dingens","Dana Arenz","Julie Overbaugh","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v11050439","link":"https://www.mdpi.com/1999-4915/11/5/439","image":"/assets/papers/2019_dingens_a.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_a.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_a.md","filePath":"papers/2019_dingens_a.md"}'),s={name:"papers/2019_dingens_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.",-1),d=[o,r];function l(c,h,u,p,f,m){return n(),i("div",null,d)}const v=t(s,[["render",l]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2019_dingens_b.md.QRcJBjnb.js b/assets/papers_2019_dingens_b.md.2fydMuAo.js
similarity index 97%
rename from assets/papers_2019_dingens_b.md.QRcJBjnb.js
rename to assets/papers_2019_dingens_b.md.2fydMuAo.js
index cd54b1f..97950d8 100644
--- a/assets/papers_2019_dingens_b.md.QRcJBjnb.js
+++ b/assets/papers_2019_dingens_b.md.2fydMuAo.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_b.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_b.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2019_dingens_b.md.QRcJBjnb.lean.js b/assets/papers_2019_dingens_b.md.2fydMuAo.lean.js
similarity index 97%
rename from assets/papers_2019_dingens_b.md.QRcJBjnb.lean.js
rename to assets/papers_2019_dingens_b.md.2fydMuAo.lean.js
index cd54b1f..97950d8 100644
--- a/assets/papers_2019_dingens_b.md.QRcJBjnb.lean.js
+++ b/assets/papers_2019_dingens_b.md.2fydMuAo.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_b.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","description":"","frontmatter":{"layout":"paper","title":"An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes","date":"2019-02-19","authors":["Adam S Dingens","Dana Arenz","Haidyn Weight","Julie Overbaugh","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2018.12.017","link":"https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub","image":"/assets/papers/2019_dingens_b.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_dingens_b.html"}]]},"headers":[],"relativePath":"papers/2019_dingens_b.md","filePath":"papers/2019_dingens_b.md"}'),s={name:"papers/2019_dingens_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.",-1),c=[o,r];function d(l,p,u,b,m,h){return n(),t("div",null,c)}const _=a(s,[["render",d]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2019_lee.md.Bqwi7pL8.js b/assets/papers_2019_lee.md.CJ7hhDFA.js
similarity index 97%
rename from assets/papers_2019_lee.md.Bqwi7pL8.js
rename to assets/papers_2019_lee.md.CJ7hhDFA.js
index 9116a07..88bb307 100644
--- a/assets/papers_2019_lee.md.Bqwi7pL8.js
+++ b/assets/papers_2019_lee.md.CJ7hhDFA.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_lee.html"}]]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_lee.html"}]]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2019_lee.md.Bqwi7pL8.lean.js b/assets/papers_2019_lee.md.CJ7hhDFA.lean.js
similarity index 97%
rename from assets/papers_2019_lee.md.Bqwi7pL8.lean.js
rename to assets/papers_2019_lee.md.CJ7hhDFA.lean.js
index 9116a07..88bb307 100644
--- a/assets/papers_2019_lee.md.Bqwi7pL8.lean.js
+++ b/assets/papers_2019_lee.md.CJ7hhDFA.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_lee.html"}]]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","description":"","frontmatter":{"layout":"paper","title":"Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin","date":"2019-08-27","authors":["Juhye M Lee","Rachel Eguia","Seth J Zost","Saket Choudhary","Patrick C Wilson","Trevor Bedford","Terry Stevens-Ayers","Michael Boeckh","Aeron C Hurt","Seema S Lakdawala","Scott E Hensley","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.49324","link":"https://elifesciences.org/articles/49324","image":"/assets/papers/2019_lee.jpg","keywords":["Influenza","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_lee.html"}]]},"headers":[],"relativePath":"papers/2019_lee.md","filePath":"papers/2019_lee.md"}'),s={name:"papers/2019_lee.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.",-1),l=[o,r];function c(u,p,d,h,m,f){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2019_machkovech.md.FdFyrCx_.js b/assets/papers_2019_machkovech.md.BJuUPLO7.js
similarity index 97%
rename from assets/papers_2019_machkovech.md.FdFyrCx_.js
rename to assets/papers_2019_machkovech.md.BJuUPLO7.js
index a07e56a..d1c54bb 100644
--- a/assets/papers_2019_machkovech.md.FdFyrCx_.js
+++ b/assets/papers_2019_machkovech.md.BJuUPLO7.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_machkovech.html"}]]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_machkovech.html"}]]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
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+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Comprehensive profiling of translation initiation in influenza virus infected cells","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of translation initiation in influenza virus infected cells","date":"2019-01-23","authors":["Heather M Machkovech","Jesse D Bloom","Arvind R Subramaniam"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1007518","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518","image":"/assets/papers/2019_machkovech.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_machkovech.html"}]]},"headers":[],"relativePath":"papers/2019_machkovech.md","filePath":"papers/2019_machkovech.md"}'),s={name:"papers/2019_machkovech.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const _=t(s,[["render",c]]);export{g as __pageData,_ as default};
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+import{_ as t,c as i,o as n,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","description":"","frontmatter":{"layout":"paper","title":"Single-cell virus sequencing of influenza infections that trigger innate immunity","date":"2019-07-15","authors":["Alistair B Russell","Elizaveta Elshina","Jacob R Kowalsky","Aartjan JW Te Velthuis","Jesse D Bloom"],"journal":"Journal of virology","doi":"10.1128/jvi.00500-19","link":"https://journals.asm.org/doi/full/10.1128/jvi.00500-19","image":"/assets/papers/2019_russell.jpg","keywords":["Influenza","Single-cell sequencing"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_russell.html"}]]},"headers":[],"relativePath":"papers/2019_russell.md","filePath":"papers/2019_russell.md"}'),a={name:"papers/2019_russell.md"},l=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.",-1),r=[l,o];function c(u,d,h,p,f,m){return n(),i("div",null,r)}const _=t(a,[["render",c]]);export{v as __pageData,_ as default};
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diff --git a/assets/papers_2019_soh.md.CC9R95ft.js b/assets/papers_2019_soh.md.ilsrMZT-.js
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+import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_soh.html"}]]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function h(p,c,u,m,d,f){return o(),t("div",null,l)}const g=a(s,[["render",h]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2019_soh.md.CC9R95ft.lean.js b/assets/papers_2019_soh.md.ilsrMZT-.lean.js
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@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_soh.html"}]]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function h(p,c,u,m,d,f){return o(),t("div",null,l)}const g=a(s,[["render",h]]);export{_ as __pageData,g as default};
+import{_ as a,c as t,o,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans","date":"2019-04-30","authors":["YQ Shirleen Soh","Louise H Moncla","Rachel Eguia","Trevor Bedford","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.45079","link":"https://doi.org/10.7554/eLife.45079","image":"/assets/papers/2019_soh.jpg","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_soh.html"}]]},"headers":[],"relativePath":"papers/2019_soh.md","filePath":"papers/2019_soh.md"}'),s={name:"papers/2019_soh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.",-1),l=[n,r];function h(p,c,u,m,d,f){return o(),t("div",null,l)}const g=a(s,[["render",h]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2019_xue_a.md.DXDEho14.js b/assets/papers_2019_xue_a.md.Z_KX1iLK.js
similarity index 97%
rename from assets/papers_2019_xue_a.md.DXDEho14.js
rename to assets/papers_2019_xue_a.md.Z_KX1iLK.js
index b3c7d34..96e0ca3 100644
--- a/assets/papers_2019_xue_a.md.DXDEho14.js
+++ b/assets/papers_2019_xue_a.md.Z_KX1iLK.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_xue_a.html"}]]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,m,p,g){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_xue_a.html"}]]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,m,p,g){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default};
diff --git a/assets/papers_2019_xue_a.md.DXDEho14.lean.js b/assets/papers_2019_xue_a.md.Z_KX1iLK.lean.js
similarity index 97%
rename from assets/papers_2019_xue_a.md.DXDEho14.lean.js
rename to assets/papers_2019_xue_a.md.Z_KX1iLK.lean.js
index b3c7d34..96e0ca3 100644
--- a/assets/papers_2019_xue_a.md.DXDEho14.lean.js
+++ b/assets/papers_2019_xue_a.md.Z_KX1iLK.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_xue_a.html"}]]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,m,p,g){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","description":"","frontmatter":{"layout":"paper","title":"Reconciling disparate estimates of viral genetic diversity during human influenza infections","date":"2019-09-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Nature genetics","doi":"10.1038/s41588-019-0349-3","link":"https://www.nature.com/articles/s41588-019-0349-3","image":"/assets/papers/2019_xue_a.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2019_xue_a.html"}]]},"headers":[],"relativePath":"papers/2019_xue_a.md","filePath":"papers/2019_xue_a.md"}'),s={name:"papers/2019_xue_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.",-1),d=[r,o];function h(l,c,u,m,p,g){return a(),i("div",null,d)}const _=t(s,[["render",h]]);export{v as __pageData,_ as default};
diff --git a/assets/papers_2020_crawford.md.Ba8D5Fgg.js b/assets/papers_2020_crawford.md.DTaQX__1.js
similarity index 97%
rename from assets/papers_2020_crawford.md.Ba8D5Fgg.js
rename to assets/papers_2020_crawford.md.DTaQX__1.js
index b6a895f..b29dff9 100644
--- a/assets/papers_2020_crawford.md.Ba8D5Fgg.js
+++ b/assets/papers_2020_crawford.md.DTaQX__1.js
@@ -1 +1 @@
-import{_ as a,c as t,o as r,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_crawford.html"}]]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return r(),t("div",null,l)}const v=a(s,[["render",d]]);export{b as __pageData,v as default};
+import{_ as a,c as t,o as r,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_crawford.html"}]]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return r(),t("div",null,l)}const v=a(s,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2020_crawford.md.Ba8D5Fgg.lean.js b/assets/papers_2020_crawford.md.DTaQX__1.lean.js
similarity index 97%
rename from assets/papers_2020_crawford.md.Ba8D5Fgg.lean.js
rename to assets/papers_2020_crawford.md.DTaQX__1.lean.js
index b6a895f..b29dff9 100644
--- a/assets/papers_2020_crawford.md.Ba8D5Fgg.lean.js
+++ b/assets/papers_2020_crawford.md.DTaQX__1.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as r,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_crawford.html"}]]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return r(),t("div",null,l)}const v=a(s,[["render",d]]);export{b as __pageData,v as default};
+import{_ as a,c as t,o as r,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","description":"","frontmatter":{"layout":"paper","title":"Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays","date":"2020-05-06","authors":["Katharine HD Crawford","Rachel Eguia","Adam S Dingens","Andrea N Loes","Keara D Malone","Caitlin R Wolf","Helen Y Chu","M Alejandra Tortorici","David Veesler","Michael Murphy","Deleah Pettie","Neil P King","Alejandro B Balazs","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12050513","link":"https://www.mdpi.com/1999-4915/12/5/513","image":"/assets/papers/2020_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_crawford.html"}]]},"headers":[],"relativePath":"papers/2020_crawford.md","filePath":"papers/2020_crawford.md"}'),s={name:"papers/2020_crawford.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.",-1),l=[o,n];function d(c,p,h,u,f,m){return r(),t("div",null,l)}const v=a(s,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2020_dingens.md.CVw-dlUS.js b/assets/papers_2020_dingens.md.0DurCBe9.js
similarity index 97%
rename from assets/papers_2020_dingens.md.CVw-dlUS.js
rename to assets/papers_2020_dingens.md.0DurCBe9.js
index 7402860..9d6f3c3 100644
--- a/assets/papers_2020_dingens.md.CVw-dlUS.js
+++ b/assets/papers_2020_dingens.md.0DurCBe9.js
@@ -1 +1 @@
-import{_ as i,c as a,o as t,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_dingens.html"}]]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return t(),a("div",null,l)}const S=i(r,[["render",d]]);export{_ as __pageData,S as default};
+import{_ as i,c as a,o as t,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_dingens.html"}]]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return t(),a("div",null,l)}const S=i(r,[["render",d]]);export{_ as __pageData,S as default};
diff --git a/assets/papers_2020_dingens.md.CVw-dlUS.lean.js b/assets/papers_2020_dingens.md.0DurCBe9.lean.js
similarity index 97%
rename from assets/papers_2020_dingens.md.CVw-dlUS.lean.js
rename to assets/papers_2020_dingens.md.0DurCBe9.lean.js
index 7402860..9d6f3c3 100644
--- a/assets/papers_2020_dingens.md.CVw-dlUS.lean.js
+++ b/assets/papers_2020_dingens.md.0DurCBe9.lean.js
@@ -1 +1 @@
-import{_ as i,c as a,o as t,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_dingens.html"}]]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return t(),a("div",null,l)}const S=i(r,[["render",d]]);export{_ as __pageData,S as default};
+import{_ as i,c as a,o as t,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","description":"","frontmatter":{"layout":"paper","title":"Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak","date":"2020-09-01","authors":["Adam S Dingens","Katharine HD Crawford","Amanda Adler","Sarah L Steele","Kirsten Lacombe","Rachel Eguia","Fatima Amanat","Alexandra C Walls","Caitlin R Wolf","Michael Murphy","Deleah Pettie","Lauren Carter","Xuan Qin","Neil P King","David Veesler","Florian Krammer","Jane A Dickerson","Helen Y Chu","Janet A Englund","Jesse D Bloom"],"journal":"Nature communications","doi":"10.1038/s41467-020-18178-1","link":"https://www.nature.com/articles/s41467-020-18178-1","image":"/assets/papers/2020_dingens.jpg","keywords":["SARS-CoV-2","Pseudovirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_dingens.html"}]]},"headers":[],"relativePath":"papers/2020_dingens.md","filePath":"papers/2020_dingens.md"}'),r={name:"papers/2020_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.",-1),l=[s,o];function d(c,h,p,u,f,m){return t(),a("div",null,l)}const S=i(r,[["render",d]]);export{_ as __pageData,S as default};
diff --git a/assets/papers_2020_einav_b.md.BuNOyH50.js b/assets/papers_2020_einav_b.md.BBCV3z5q.js
similarity index 97%
rename from assets/papers_2020_einav_b.md.BuNOyH50.js
rename to assets/papers_2020_einav_b.md.BBCV3z5q.js
index a0376a2..ea78c31 100644
--- a/assets/papers_2020_einav_b.md.BuNOyH50.js
+++ b/assets/papers_2020_einav_b.md.BBCV3z5q.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_einav_b.html"}]]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default};
+import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_einav_b.html"}]]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2020_einav_b.md.BuNOyH50.lean.js b/assets/papers_2020_einav_b.md.BBCV3z5q.lean.js
similarity index 97%
rename from assets/papers_2020_einav_b.md.BuNOyH50.lean.js
rename to assets/papers_2020_einav_b.md.BBCV3z5q.lean.js
index a0376a2..ea78c31 100644
--- a/assets/papers_2020_einav_b.md.BuNOyH50.lean.js
+++ b/assets/papers_2020_einav_b.md.BBCV3z5q.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_einav_b.html"}]]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default};
+import{_ as t,c as a,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"When two are better than one: Modeling the mechanisms of antibody mixtures","description":"","frontmatter":{"layout":"paper","title":"When two are better than one: Modeling the mechanisms of antibody mixtures","date":"2020-05-04","authors":["Tal Einav","Jesse D Bloom"],"journal":"PLoS computational biology","doi":"10.1371/journal.pcbi.1007830","link":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830","image":"/assets/papers/2020_einav_b.png","keywords":["Modeling","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_einav_b.html"}]]},"headers":[],"relativePath":"papers/2020_einav_b.md","filePath":"papers/2020_einav_b.md"}'),n={name:"papers/2020_einav_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.",-1),d=[r,s];function l(c,h,p,m,b,u){return i(),a("div",null,d)}const g=t(n,[["render",l]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2020_gentles.md.4SSt6wXx.js b/assets/papers_2020_gentles.md.ninz-r-5.js
similarity index 97%
rename from assets/papers_2020_gentles.md.4SSt6wXx.js
rename to assets/papers_2020_gentles.md.ninz-r-5.js
index 98cdeec..fc4ac97 100644
--- a/assets/papers_2020_gentles.md.4SSt6wXx.js
+++ b/assets/papers_2020_gentles.md.ninz-r-5.js
@@ -1 +1 @@
-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_gentles.html"}]]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,p,u,h,b,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default};
+import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_gentles.html"}]]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,p,u,h,b,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default};
diff --git a/assets/papers_2020_gentles.md.4SSt6wXx.lean.js b/assets/papers_2020_gentles.md.ninz-r-5.lean.js
similarity index 97%
rename from assets/papers_2020_gentles.md.4SSt6wXx.lean.js
rename to assets/papers_2020_gentles.md.ninz-r-5.lean.js
index 98cdeec..fc4ac97 100644
--- a/assets/papers_2020_gentles.md.4SSt6wXx.lean.js
+++ b/assets/papers_2020_gentles.md.ninz-r-5.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_gentles.html"}]]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,p,u,h,b,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default};
+import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","description":"","frontmatter":{"layout":"paper","title":"Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding","date":"2020-05-30","authors":["Lauren E Gentles","Hongquan Wan","Maryna C Eichelberger","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12060597","link":"https://www.mdpi.com/1999-4915/12/6/597","image":"/assets/papers/2020_gentles.png","keywords":["Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_gentles.html"}]]},"headers":[],"relativePath":"papers/2020_gentles.md","filePath":"papers/2020_gentles.md"}'),s={name:"papers/2020_gentles.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.",-1),l=[o,r];function c(d,p,u,h,b,f){return n(),i("div",null,l)}const y=t(s,[["render",c]]);export{m as __pageData,y as default};
diff --git a/assets/papers_2020_hilton.md.2O2maEDV.js b/assets/papers_2020_hilton.md.CDgvg1-O.js
similarity index 95%
rename from assets/papers_2020_hilton.md.2O2maEDV.js
rename to assets/papers_2020_hilton.md.CDgvg1-O.js
index ab3876e..e464a23 100644
--- a/assets/papers_2020_hilton.md.2O2maEDV.js
+++ b/assets/papers_2020_hilton.md.CDgvg1-O.js
@@ -1 +1 @@
-import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_hilton.html"}]]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,f){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default};
+import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_hilton.html"}]]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,f){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2020_hilton.md.2O2maEDV.lean.js b/assets/papers_2020_hilton.md.CDgvg1-O.lean.js
similarity index 95%
rename from assets/papers_2020_hilton.md.2O2maEDV.lean.js
rename to assets/papers_2020_hilton.md.CDgvg1-O.lean.js
index ab3876e..e464a23 100644
--- a/assets/papers_2020_hilton.md.2O2maEDV.lean.js
+++ b/assets/papers_2020_hilton.md.CDgvg1-O.lean.js
@@ -1 +1 @@
-import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_hilton.html"}]]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,f){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default};
+import{_ as a,c as o,o as s,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"dms-view: Interactive visualization tool for deep mutational scanning data","description":"","frontmatter":{"layout":"paper","title":"dms-view: Interactive visualization tool for deep mutational scanning data","date":"2020-08-17","authors":["Sarah K Hilton*","John Huddleston*","Allison Black","Khrystyna North","Adam S Dingens","Trevor Bedford","Jesse D Bloom"],"journal":"JOSS","doi":"10.21105/joss.02353","link":"https://joss.theoj.org/papers/10.21105/joss.02353","image":"/assets/papers/2020_hilton.png","keywords":["Deep mutational scanning","Software tools"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_hilton.html"}]]},"headers":[],"relativePath":"papers/2020_hilton.md","filePath":"papers/2020_hilton.md"}'),r={name:"papers/2020_hilton.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,[t("Here we describe dms-view ("),e("a",{href:"https://dms-view.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-view.github.io/"),t("), a flexible, web-based, interactive visualization tool for DMS data.")],-1),l=[i,n];function d(c,p,h,_,m,f){return s(),o("div",null,l)}const v=a(r,[["render",d]]);export{b as __pageData,v as default};
diff --git a/assets/papers_2020_loes.md.qFSUDqTw.js b/assets/papers_2020_loes.md.Dtg8OATQ.js
similarity index 97%
rename from assets/papers_2020_loes.md.qFSUDqTw.js
rename to assets/papers_2020_loes.md.Dtg8OATQ.js
index e5f7c86..de43853 100644
--- a/assets/papers_2020_loes.md.qFSUDqTw.js
+++ b/assets/papers_2020_loes.md.Dtg8OATQ.js
@@ -1 +1 @@
-import{_ as a,c as i,o as n,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_loes.html"}]]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),l=[o,r];function c(d,u,p,h,f,m){return n(),i("div",null,l)}const _=a(s,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as a,c as i,o as n,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_loes.html"}]]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),l=[o,r];function c(d,u,p,h,f,m){return n(),i("div",null,l)}const _=a(s,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2020_loes.md.qFSUDqTw.lean.js b/assets/papers_2020_loes.md.Dtg8OATQ.lean.js
similarity index 97%
rename from assets/papers_2020_loes.md.qFSUDqTw.lean.js
rename to assets/papers_2020_loes.md.Dtg8OATQ.lean.js
index e5f7c86..de43853 100644
--- a/assets/papers_2020_loes.md.qFSUDqTw.lean.js
+++ b/assets/papers_2020_loes.md.Dtg8OATQ.lean.js
@@ -1 +1 @@
-import{_ as a,c as i,o as n,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_loes.html"}]]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),l=[o,r];function c(d,u,p,h,f,m){return n(),i("div",null,l)}const _=a(s,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as a,c as i,o as n,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","description":"","frontmatter":{"layout":"paper","title":"Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice","date":"2020-09-05","authors":["Andrea N Loes","Lauren E Gentles","Allison J Greaney","Katharine HD Crawford","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v12090987","link":"https://www.mdpi.com/1999-4915/12/9/987","image":"/assets/papers/2020_loes.jpg","keywords":["SARS-CoV-2","Influenza","Vaccines"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_loes.html"}]]},"headers":[],"relativePath":"papers/2020_loes.md","filePath":"papers/2020_loes.md"}'),s={name:"papers/2020_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.",-1),l=[o,r];function c(d,u,p,h,f,m){return n(),i("div",null,l)}const _=a(s,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2020_roop.md.b8JCN22x.js b/assets/papers_2020_roop.md.DX7PtOp1.js
similarity index 97%
rename from assets/papers_2020_roop.md.b8JCN22x.js
rename to assets/papers_2020_roop.md.DX7PtOp1.js
index 3f8df39..f08c113 100644
--- a/assets/papers_2020_roop.md.b8JCN22x.js
+++ b/assets/papers_2020_roop.md.DX7PtOp1.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_roop.html"}]]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,l,m,p,h,f){return n(),a("div",null,c)}const _=t(i,[["render",d]]);export{y as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_roop.html"}]]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,l,m,p,h,f){return n(),a("div",null,c)}const _=t(i,[["render",d]]);export{y as __pageData,_ as default};
diff --git a/assets/papers_2020_roop.md.b8JCN22x.lean.js b/assets/papers_2020_roop.md.DX7PtOp1.lean.js
similarity index 97%
rename from assets/papers_2020_roop.md.b8JCN22x.lean.js
rename to assets/papers_2020_roop.md.DX7PtOp1.lean.js
index 3f8df39..f08c113 100644
--- a/assets/papers_2020_roop.md.b8JCN22x.lean.js
+++ b/assets/papers_2020_roop.md.DX7PtOp1.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_roop.html"}]]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,l,m,p,h,f){return n(),a("div",null,c)}const _=t(i,[["render",d]]);export{y as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","description":"","frontmatter":{"layout":"paper","title":"Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5","date":"2020-02-21","authors":["Jeremy I Roop","Noah A Cassidy","Adam S Dingens","Jesse D Bloom","Julie Overbaugh"],"journal":"Viruses","doi":"10.3390/v12020241","link":"https://www.mdpi.com/1999-4915/12/2/241","image":"/assets/papers/2020_roop.jpg","keywords":["HIV"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_roop.html"}]]},"headers":[],"relativePath":"papers/2020_roop.md","filePath":"papers/2020_roop.md"}'),i={name:"papers/2020_roop.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.",-1),c=[s,r];function d(u,l,m,p,h,f){return n(),a("div",null,c)}const _=t(i,[["render",d]]);export{y as __pageData,_ as default};
diff --git a/assets/papers_2020_starr_a.md.C3fMsw5D.js b/assets/papers_2020_starr_a.md.CkuX11AK.js
similarity index 97%
rename from assets/papers_2020_starr_a.md.C3fMsw5D.js
rename to assets/papers_2020_starr_a.md.CkuX11AK.js
index 4f983ce..f95a460 100644
--- a/assets/papers_2020_starr_a.md.C3fMsw5D.js
+++ b/assets/papers_2020_starr_a.md.CkuX11AK.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_starr_a.html"}]]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),l=[o,s];function d(c,p,f,m,h,u){return n(),t("div",null,l)}const b=a(r,[["render",d]]);export{g as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_starr_a.html"}]]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),l=[o,s];function d(c,p,f,m,h,u){return n(),t("div",null,l)}const b=a(r,[["render",d]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2020_starr_a.md.C3fMsw5D.lean.js b/assets/papers_2020_starr_a.md.CkuX11AK.lean.js
similarity index 97%
rename from assets/papers_2020_starr_a.md.C3fMsw5D.lean.js
rename to assets/papers_2020_starr_a.md.CkuX11AK.lean.js
index 4f983ce..f95a460 100644
--- a/assets/papers_2020_starr_a.md.C3fMsw5D.lean.js
+++ b/assets/papers_2020_starr_a.md.CkuX11AK.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_starr_a.html"}]]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),l=[o,s];function d(c,p,f,m,h,u){return n(),t("div",null,l)}const b=a(r,[["render",d]]);export{g as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","date":"2020-09-03","authors":["Tyler N Starr*","Allison J Greaney*","Sarah K Hilton","Daniel Ellis","Katharine HD Crawford","Adam S Dingens","Mary Jane Navarro","John E Bowen","Alejandra M Tortorici","Alexandra C Walls","Neil P King","David Veesler","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2020.08.012","link":"https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub","image":"/assets/papers/2020_starr_a.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_starr_a.html"}]]},"headers":[],"relativePath":"papers/2020_starr_a.md","filePath":"papers/2020_starr_a.md"}'),r={name:"papers/2020_starr_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.",-1),l=[o,s];function d(c,p,f,m,h,u){return n(),t("div",null,l)}const b=a(r,[["render",d]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2020_xue.md.CWclfT2U.js b/assets/papers_2020_xue.md.Dg6X1ZVo.js
similarity index 97%
rename from assets/papers_2020_xue.md.CWclfT2U.js
rename to assets/papers_2020_xue.md.Dg6X1ZVo.js
index f0853f3..1cc8b3a 100644
--- a/assets/papers_2020_xue.md.CWclfT2U.js
+++ b/assets/papers_2020_xue.md.Dg6X1ZVo.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_xue.html"}]]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,p,m,v){return n(),a("div",null,l)}const g=t(s,[["render",h]]);export{_ as __pageData,g as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_xue.html"}]]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,p,m,v){return n(),a("div",null,l)}const g=t(s,[["render",h]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2020_xue.md.CWclfT2U.lean.js b/assets/papers_2020_xue.md.Dg6X1ZVo.lean.js
similarity index 97%
rename from assets/papers_2020_xue.md.CWclfT2U.lean.js
rename to assets/papers_2020_xue.md.Dg6X1ZVo.lean.js
index f0853f3..1cc8b3a 100644
--- a/assets/papers_2020_xue.md.CWclfT2U.lean.js
+++ b/assets/papers_2020_xue.md.Dg6X1ZVo.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_xue.html"}]]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,p,m,v){return n(),a("div",null,l)}const g=t(s,[["render",h]]);export{_ as __pageData,g as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Linking influenza virus evolution within and between human hosts","description":"","frontmatter":{"layout":"paper","title":"Linking influenza virus evolution within and between human hosts","date":"2020-01-01","authors":["Katherine S Xue","Jesse D Bloom"],"journal":"Virus evolution","doi":"10.1093/ve/veaa010","link":"https://academic.oup.com/ve/article/6/1/veaa010/5739536","image":"/assets/papers/2020_xue.jpg","keywords":["Influenza","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2020_xue.html"}]]},"headers":[],"relativePath":"papers/2020_xue.md","filePath":"papers/2020_xue.md"}'),s={name:"papers/2020_xue.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.",-1),l=[o,r];function h(c,u,d,p,m,v){return n(),a("div",null,l)}const g=t(s,[["render",h]]);export{_ as __pageData,g as default};
diff --git a/assets/papers_2021_bloom_a.md.DHMEyKa_.js b/assets/papers_2021_bloom_a.md.BVX6hzmG.js
similarity index 93%
rename from assets/papers_2021_bloom_a.md.DHMEyKa_.js
rename to assets/papers_2021_bloom_a.md.BVX6hzmG.js
index 326bdd5..6ad96f9 100644
--- a/assets/papers_2021_bloom_a.md.DHMEyKa_.js
+++ b/assets/papers_2021_bloom_a.md.BVX6hzmG.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),s={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),l=[n,i];function d(c,h,m,p,u,_){return o(),t("div",null,l)}const y=a(s,[["render",d]]);export{b as __pageData,y as default};
+import{_ as a,c as t,o,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),s={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),l=[n,i];function d(c,h,m,p,u,_){return o(),t("div",null,l)}const y=a(s,[["render",d]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2021_bloom_a.md.DHMEyKa_.lean.js b/assets/papers_2021_bloom_a.md.BVX6hzmG.lean.js
similarity index 93%
rename from assets/papers_2021_bloom_a.md.DHMEyKa_.lean.js
rename to assets/papers_2021_bloom_a.md.BVX6hzmG.lean.js
index 326bdd5..6ad96f9 100644
--- a/assets/papers_2021_bloom_a.md.DHMEyKa_.lean.js
+++ b/assets/papers_2021_bloom_a.md.BVX6hzmG.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),s={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),l=[n,i];function d(c,h,m,p,u,_){return o(),t("div",null,l)}const y=a(s,[["render",d]]);export{b as __pageData,y as default};
+import{_ as a,c as t,o,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","description":"","frontmatter":{"layout":"paper","title":"Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic","date":"2021-12-01","authors":["Jesse D Bloom"],"journal":"mBio","doi":"10.1093/molbev/msab246","link":"https://academic.oup.com/mbe/article/38/12/5211/6353034","image":"/assets/papers/2021_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2021_bloom_a.md","filePath":"papers/2021_bloom_a.md"}'),s={name:"papers/2021_bloom_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.",-1),l=[n,i];function d(c,h,m,p,u,_){return o(),t("div",null,l)}const y=a(s,[["render",d]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2021_crawford.md.CPfuszX0.js b/assets/papers_2021_crawford.md.pvTs3b9Y.js
similarity index 97%
rename from assets/papers_2021_crawford.md.CPfuszX0.js
rename to assets/papers_2021_crawford.md.pvTs3b9Y.js
index 271e6d0..27be546 100644
--- a/assets/papers_2021_crawford.md.CPfuszX0.js
+++ b/assets/papers_2021_crawford.md.pvTs3b9Y.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_crawford.html"}]]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,h,u){return i(),t("div",null,d)}const _=a(r,[["render",l]]);export{b as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_crawford.html"}]]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,h,u){return i(),t("div",null,d)}const _=a(r,[["render",l]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_crawford.md.CPfuszX0.lean.js b/assets/papers_2021_crawford.md.pvTs3b9Y.lean.js
similarity index 97%
rename from assets/papers_2021_crawford.md.CPfuszX0.lean.js
rename to assets/papers_2021_crawford.md.pvTs3b9Y.lean.js
index 271e6d0..27be546 100644
--- a/assets/papers_2021_crawford.md.CPfuszX0.lean.js
+++ b/assets/papers_2021_crawford.md.pvTs3b9Y.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_crawford.html"}]]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,h,u){return i(),t("div",null,d)}const _=a(r,[["render",l]]);export{b as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","description":"","frontmatter":{"layout":"paper","title":"Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection","date":"2021-01-15","authors":["Katharine HD Crawford","Adam S Dingens","Rachel Eguia","Caitlin R Wolf","Naomi Wilcox","Jennifer K Logue","Kiel Shuey","Amanda M Casto","Brooke Fiala","Samuel Wrenn","Deleah Pettie","Neil P King","Alexander L Greninger","Helen Y Chu","Jesse D Bloom"],"journal":"The Journal of infectious diseases","doi":"10.1093/infdis/jiaa618","link":"https://academic.oup.com/jid/article/223/2/197/5916372","image":"/assets/papers/2021_crawford.jpg","keywords":["SARS-CoV-2","Immunity","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_crawford.html"}]]},"headers":[],"relativePath":"papers/2021_crawford.md","filePath":"papers/2021_crawford.md"}'),r={name:"papers/2021_crawford.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.",-1),d=[n,s];function l(c,m,p,f,h,u){return i(),t("div",null,d)}const _=a(r,[["render",l]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_dingens.md.Dvz1NmZZ.js b/assets/papers_2021_dingens.md.B8pvbsXn.js
similarity index 97%
rename from assets/papers_2021_dingens.md.Dvz1NmZZ.js
rename to assets/papers_2021_dingens.md.B8pvbsXn.js
index c26c3d8..0ebbc4f 100644
--- a/assets/papers_2021_dingens.md.Dvz1NmZZ.js
+++ b/assets/papers_2021_dingens.md.B8pvbsXn.js
@@ -1 +1 @@
-import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_dingens.html"}]]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,h,m,f,g){return a(),n("div",null,l)}const _=i(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_dingens.html"}]]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,h,m,f,g){return a(),n("div",null,l)}const _=i(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_dingens.md.Dvz1NmZZ.lean.js b/assets/papers_2021_dingens.md.B8pvbsXn.lean.js
similarity index 97%
rename from assets/papers_2021_dingens.md.Dvz1NmZZ.lean.js
rename to assets/papers_2021_dingens.md.B8pvbsXn.lean.js
index c26c3d8..0ebbc4f 100644
--- a/assets/papers_2021_dingens.md.Dvz1NmZZ.lean.js
+++ b/assets/papers_2021_dingens.md.B8pvbsXn.lean.js
@@ -1 +1 @@
-import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_dingens.html"}]]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,h,m,f,g){return a(),n("div",null,l)}const _=i(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","description":"","frontmatter":{"layout":"paper","title":"High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination","date":"2021-01-13","authors":["Adam S Dingens","Payal Pratap","Keara Malone","Sarah K Hilton","Thomas Ketas","Christopher A Cottrell","Julie Overbaugh","John P Moore","PJ Klasse","Andrew B Ward","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.64281","link":"https://elifesciences.org/articles/64281","image":"/assets/papers/2021_dingens.jpg","keywords":["HIV","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_dingens.html"}]]},"headers":[],"relativePath":"papers/2021_dingens.md","filePath":"papers/2021_dingens.md"}'),o={name:"papers/2021_dingens.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.",-1),l=[s,r];function c(d,p,h,m,f,g){return a(),n("div",null,l)}const _=i(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_eguia.md.DpKzVauA.js b/assets/papers_2021_eguia.md.DgFqtJ8C.js
similarity index 97%
rename from assets/papers_2021_eguia.md.DpKzVauA.js
rename to assets/papers_2021_eguia.md.DgFqtJ8C.js
index e921227..dd1daae 100644
--- a/assets/papers_2021_eguia.md.DpKzVauA.js
+++ b/assets/papers_2021_eguia.md.DgFqtJ8C.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_eguia.html"}]]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_eguia.html"}]]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2021_eguia.md.DpKzVauA.lean.js b/assets/papers_2021_eguia.md.DgFqtJ8C.lean.js
similarity index 97%
rename from assets/papers_2021_eguia.md.DpKzVauA.lean.js
rename to assets/papers_2021_eguia.md.DgFqtJ8C.lean.js
index e921227..dd1daae 100644
--- a/assets/papers_2021_eguia.md.DpKzVauA.lean.js
+++ b/assets/papers_2021_eguia.md.DgFqtJ8C.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_eguia.html"}]]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A human coronavirus evolves antigenically to escape antibody immunity","description":"","frontmatter":{"layout":"paper","title":"A human coronavirus evolves antigenically to escape antibody immunity","date":"2021-04-08","authors":["Rachel T Eguia","Katharine HD Crawford","Terry Stevens-Ayers","Laurel Kelnhofer-Millevolte","Alexander L Greninger","Janet A Englund","Michael J Boeckh","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1009453","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453","image":"/assets/papers/2021_eguia.png","keywords":["Coronavirus","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_eguia.html"}]]},"headers":[],"relativePath":"papers/2021_eguia.md","filePath":"papers/2021_eguia.md"}'),o={name:"papers/2021_eguia.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.",-1),l=[r,n];function c(u,d,h,p,m,v){return i(),t("div",null,l)}const _=a(o,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2021_greaney_a.md.Cv4Mdsid.js b/assets/papers_2021_greaney_a.md.n1sxaj-W.js
similarity index 97%
rename from assets/papers_2021_greaney_a.md.Cv4Mdsid.js
rename to assets/papers_2021_greaney_a.md.n1sxaj-W.js
index a0c1dd6..f9a79b0 100644
--- a/assets/papers_2021_greaney_a.md.Cv4Mdsid.js
+++ b/assets/papers_2021_greaney_a.md.n1sxaj-W.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default};
+import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2021_greaney_a.md.Cv4Mdsid.lean.js b/assets/papers_2021_greaney_a.md.n1sxaj-W.lean.js
similarity index 97%
rename from assets/papers_2021_greaney_a.md.Cv4Mdsid.lean.js
rename to assets/papers_2021_greaney_a.md.n1sxaj-W.lean.js
index a0c1dd6..f9a79b0 100644
--- a/assets/papers_2021_greaney_a.md.Cv4Mdsid.lean.js
+++ b/assets/papers_2021_greaney_a.md.n1sxaj-W.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default};
+import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","description":"","frontmatter":{"layout":"paper","title":"Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies","date":"2021-07-07","authors":["Allison J Greaney","Tyler N Starr","Christopher O Barnes","Yiska Weisblum","Fabian Schmidt","Marina Caskey","Christian Gaebler","Alice Cho","Marianna Agudelo","Shlomo Finkin","Zijun Wang","Daniel Poston","Frauke Muecksch","Theodora Hatziioannou","Paul D Bieniasz","Davide F Robbiani","Michel C Nussenzweig","Pamela J Bjorkman","Jesse D Bloom"],"journal":"Nature Communications","doi":"10.1038/s41467-021-24435-8","link":"https://www.nature.com/articles/s41467-021-24435-8","image":"/assets/papers/2021_greaney_a.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_a.md","filePath":"papers/2021_greaney_a.md"}'),o={name:"papers/2021_greaney_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.",-1),l=[n,r];function p(c,d,h,m,u,b){return s(),t("div",null,l)}const y=a(o,[["render",p]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2021_greaney_b.md.BrDcYLWl.js b/assets/papers_2021_greaney_b.md.4YTYSLE-.js
similarity index 97%
rename from assets/papers_2021_greaney_b.md.BrDcYLWl.js
rename to assets/papers_2021_greaney_b.md.4YTYSLE-.js
index eddc66f..72afe58 100644
--- a/assets/papers_2021_greaney_b.md.BrDcYLWl.js
+++ b/assets/papers_2021_greaney_b.md.4YTYSLE-.js
@@ -1 +1 @@
-import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,y){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default};
+import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,y){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2021_greaney_b.md.BrDcYLWl.lean.js b/assets/papers_2021_greaney_b.md.4YTYSLE-.lean.js
similarity index 97%
rename from assets/papers_2021_greaney_b.md.BrDcYLWl.lean.js
rename to assets/papers_2021_greaney_b.md.4YTYSLE-.lean.js
index eddc66f..72afe58 100644
--- a/assets/papers_2021_greaney_b.md.BrDcYLWl.lean.js
+++ b/assets/papers_2021_greaney_b.md.4YTYSLE-.lean.js
@@ -1 +1 @@
-import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,y){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default};
+import{_ as i,c as t,o as a,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","description":"","frontmatter":{"layout":"paper","title":"Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection","date":"2021-06-30","authors":["Allison J Greaney","Andrea N Loes","Lauren E Gentles","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Science translational medicine","doi":"10.1126/scitranslmed.abi9915","link":"https://www.science.org/doi/full/10.1126/scitranslmed.abi9915","image":"/assets/papers/2021_greaney_b.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_b.md","filePath":"papers/2021_greaney_b.md"}'),n={name:"papers/2021_greaney_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.",-1),c=[r,s];function d(l,b,p,m,h,y){return a(),t("div",null,c)}const _=i(n,[["render",d]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2021_greaney_c.md.BqHdlmdp.js b/assets/papers_2021_greaney_c.md.BwSO6yeP.js
similarity index 97%
rename from assets/papers_2021_greaney_c.md.BqHdlmdp.js
rename to assets/papers_2021_greaney_c.md.BwSO6yeP.js
index 733c38d..cecaba0 100644
--- a/assets/papers_2021_greaney_c.md.BqHdlmdp.js
+++ b/assets/papers_2021_greaney_c.md.BwSO6yeP.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,p,d,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,p,d,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2021_greaney_c.md.BqHdlmdp.lean.js b/assets/papers_2021_greaney_c.md.BwSO6yeP.lean.js
similarity index 97%
rename from assets/papers_2021_greaney_c.md.BqHdlmdp.lean.js
rename to assets/papers_2021_greaney_c.md.BwSO6yeP.lean.js
index 733c38d..cecaba0 100644
--- a/assets/papers_2021_greaney_c.md.BqHdlmdp.lean.js
+++ b/assets/papers_2021_greaney_c.md.BwSO6yeP.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,p,d,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","description":"","frontmatter":{"layout":"paper","title":"Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies","date":"2021-03-10","authors":["Allison J Greaney","Andrea N Loes","Katharine HD Crawford","Tyler N Starr","Keara D Malone","Helen Y Chu","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2021.02.003","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf","image":"/assets/papers/2021_greaney_c.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_c.md","filePath":"papers/2021_greaney_c.md"}'),o={name:"papers/2021_greaney_c.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.",-1),l=[s,r];function c(m,p,d,h,u,b){return i(),t("div",null,l)}const y=a(o,[["render",c]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2021_greaney_d.md.DFxOA2xP.js b/assets/papers_2021_greaney_d.md.Cpad738E.js
similarity index 97%
rename from assets/papers_2021_greaney_d.md.DFxOA2xP.js
rename to assets/papers_2021_greaney_d.md.Cpad738E.js
index 511e9c6..f7d5fc9 100644
--- a/assets/papers_2021_greaney_d.md.DFxOA2xP.js
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-import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_d.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default};
+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_d.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default};
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rename to assets/papers_2021_greaney_d.md.Cpad738E.lean.js
index 511e9c6..f7d5fc9 100644
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+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","description":"","frontmatter":{"layout":"paper","title":"Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition","date":"2021-01-13","authors":["Allison J Greaney*","Tyler N Starr*","Pavlo Gilchuk","Seth J Zost","Elad Binshtein","Andrea N Loes","Sarah K Hilton","John Huddleston","Rachel Eguia","Katharine HD Crawford","Adam S Dingens","Rachel S Nargi","Rachel E Sutton","Naveenchandra Suryadevara","Paul W Rothlauf","Zhuoming Liu","Sean PJ Whelan","Robert H Carnahan","James E Crowe","Jesse D Bloom"],"journal":"Cell host & microbe","doi":"10.1016/j.chom.2020.11.007","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf","image":"/assets/papers/2021_greaney_d.jpg","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_d.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_d.md","filePath":"papers/2021_greaney_d.md"}'),i={name:"papers/2021_greaney_d.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.",-1),c=[s,r];function d(l,p,h,m,u,g){return n(),t("div",null,c)}const _=a(i,[["render",d]]);export{f as __pageData,_ as default};
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similarity index 95%
rename from assets/papers_2021_greaney_welsh.md.DB2moYJL.js
rename to assets/papers_2021_greaney_welsh.md.CZZMyr6j.js
index d783d78..02e2ecb 100644
--- a/assets/papers_2021_greaney_welsh.md.DB2moYJL.js
+++ b/assets/papers_2021_greaney_welsh.md.CZZMyr6j.js
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-import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_welsh.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),r={name:"papers/2021_greaney_welsh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[n,o];function c(m,p,d,h,u,_){return s(),a("div",null,l)}const v=t(r,[["render",c]]);export{y as __pageData,v as default};
+import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_welsh.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),r={name:"papers/2021_greaney_welsh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[n,o];function c(m,p,d,h,u,_){return s(),a("div",null,l)}const v=t(r,[["render",c]]);export{y as __pageData,v as default};
diff --git a/assets/papers_2021_greaney_welsh.md.DB2moYJL.lean.js b/assets/papers_2021_greaney_welsh.md.CZZMyr6j.lean.js
similarity index 95%
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rename to assets/papers_2021_greaney_welsh.md.CZZMyr6j.lean.js
index d783d78..02e2ecb 100644
--- a/assets/papers_2021_greaney_welsh.md.DB2moYJL.lean.js
+++ b/assets/papers_2021_greaney_welsh.md.CZZMyr6j.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_welsh.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),r={name:"papers/2021_greaney_welsh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[n,o];function c(m,p,d,h,u,_){return s(),a("div",null,l)}const v=t(r,[["render",c]]);export{y as __pageData,v as default};
+import{_ as t,c as a,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","description":"","frontmatter":{"layout":"paper","title":"Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution","date":"2021-04-20","authors":["Allison J Greaney","Frances C Welsh","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100257","link":"https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub","image":"/assets/papers/2021_greaney_welsh.jpg","keywords":["Measles","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_greaney_welsh.html"}]]},"headers":[],"relativePath":"papers/2021_greaney_welsh.md","filePath":"papers/2021_greaney_welsh.md"}'),r={name:"papers/2021_greaney_welsh.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.",-1),l=[n,o];function c(m,p,d,h,u,_){return s(),a("div",null,l)}const v=t(r,[["render",c]]);export{y as __pageData,v as default};
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similarity index 97%
rename from assets/papers_2021_soh.md.DSFskWX9.js
rename to assets/papers_2021_soh.md.B1rHTGrn.js
index f66bced..c2de528 100644
--- a/assets/papers_2021_soh.md.DSFskWX9.js
+++ b/assets/papers_2021_soh.md.B1rHTGrn.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_soh.html"}]]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),i("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_soh.html"}]]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),i("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_soh.md.DSFskWX9.lean.js b/assets/papers_2021_soh.md.B1rHTGrn.lean.js
similarity index 97%
rename from assets/papers_2021_soh.md.DSFskWX9.lean.js
rename to assets/papers_2021_soh.md.B1rHTGrn.lean.js
index f66bced..c2de528 100644
--- a/assets/papers_2021_soh.md.DSFskWX9.lean.js
+++ b/assets/papers_2021_soh.md.B1rHTGrn.lean.js
@@ -1 +1 @@
-import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_soh.html"}]]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),i("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as t,c as i,o as a,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","description":"","frontmatter":{"layout":"paper","title":"Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir","date":"2021-06-22","authors":["Shirleen YQ Soh","Keara D Malone","Rachel T Eguia","Jesse D Bloom"],"journal":"Viruses","doi":"10.3390/v13071196","link":"https://www.mdpi.com/1999-4915/13/7/1196","image":"/assets/papers/2021_soh.png","keywords":["Influenza","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_soh.html"}]]},"headers":[],"relativePath":"papers/2021_soh.md","filePath":"papers/2021_soh.md"}'),o={name:"papers/2021_soh.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.",-1),l=[s,r];function c(d,p,h,m,u,f){return a(),i("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2021_starr_b.md.Bez2T6k3.js b/assets/papers_2021_starr_b.md.xoEX3T3A.js
similarity index 94%
rename from assets/papers_2021_starr_b.md.Bez2T6k3.js
rename to assets/papers_2021_starr_b.md.xoEX3T3A.js
index 5d0cecf..569452c 100644
--- a/assets/papers_2021_starr_b.md.Bez2T6k3.js
+++ b/assets/papers_2021_starr_b.md.xoEX3T3A.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_b.html"}]]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,_){return o(),a("div",null,c)}const g=t(n,[["render",l]]);export{f as __pageData,g as default};
+import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_b.html"}]]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,_){return o(),a("div",null,c)}const g=t(n,[["render",l]]);export{f as __pageData,g as default};
diff --git a/assets/papers_2021_starr_b.md.Bez2T6k3.lean.js b/assets/papers_2021_starr_b.md.xoEX3T3A.lean.js
similarity index 94%
rename from assets/papers_2021_starr_b.md.Bez2T6k3.lean.js
rename to assets/papers_2021_starr_b.md.xoEX3T3A.lean.js
index 5d0cecf..569452c 100644
--- a/assets/papers_2021_starr_b.md.Bez2T6k3.lean.js
+++ b/assets/papers_2021_starr_b.md.xoEX3T3A.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_b.html"}]]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,_){return o(),a("div",null,c)}const g=t(n,[["render",l]]);export{f as __pageData,g as default};
+import{_ as t,c as a,o,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","description":"","frontmatter":{"layout":"paper","title":"Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016","date":"2021-04-20","authors":["Tyler N Starr","Allison J Greaney","Adam S Dingens","Jesse D Bloom"],"journal":"Cell Reports Medicine","doi":"10.1016/j.xcrm.2021.100255","link":"https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf","image":"/assets/papers/2021_starr_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_b.html"}]]},"headers":[],"relativePath":"papers/2021_starr_b.md","filePath":"papers/2021_starr_b.md"}'),n={name:"papers/2021_starr_b.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.",-1),c=[s,r];function l(d,p,m,h,b,_){return o(),a("div",null,c)}const g=t(n,[["render",l]]);export{f as __pageData,g as default};
diff --git a/assets/papers_2021_starr_greaney.md.DuXM9BQL.js b/assets/papers_2021_starr_greaney.md.BMKjaYQD.js
similarity index 97%
rename from assets/papers_2021_starr_greaney.md.DuXM9BQL.js
rename to assets/papers_2021_starr_greaney.md.BMKjaYQD.js
index 56363cf..dfe6e1c 100644
--- a/assets/papers_2021_starr_greaney.md.DuXM9BQL.js
+++ b/assets/papers_2021_starr_greaney.md.BMKjaYQD.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_greaney.html"}]]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(p,d,h,m,u,_){return s(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default};
+import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_greaney.html"}]]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(p,d,h,m,u,_){return s(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2021_starr_greaney.md.DuXM9BQL.lean.js b/assets/papers_2021_starr_greaney.md.BMKjaYQD.lean.js
similarity index 97%
rename from assets/papers_2021_starr_greaney.md.DuXM9BQL.lean.js
rename to assets/papers_2021_starr_greaney.md.BMKjaYQD.lean.js
index 56363cf..dfe6e1c 100644
--- a/assets/papers_2021_starr_greaney.md.DuXM9BQL.lean.js
+++ b/assets/papers_2021_starr_greaney.md.BMKjaYQD.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_greaney.html"}]]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(p,d,h,m,u,_){return s(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default};
+import{_ as a,c as t,o as s,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","description":"","frontmatter":{"layout":"paper","title":"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19","date":"2021-02-19","authors":["Tyler N Starr*","Allison J Greaney*","Amin Addetia","William W Hannon","Manish C Choudhary","Adam S Dingens","Jonathan Z Li","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abf9302","link":"https://www.science.org/doi/full/10.1126/science.abf9302","image":"/assets/papers/2021_starr_greaney.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2021_starr_greaney.html"}]]},"headers":[],"relativePath":"papers/2021_starr_greaney.md","filePath":"papers/2021_starr_greaney.md"}'),n={name:"papers/2021_starr_greaney.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),o=e("p",null,"Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.",-1),c=[r,o];function l(p,d,h,m,u,_){return s(),t("div",null,c)}const b=a(n,[["render",l]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2021_starr_greaney_a.md.CXuiZgBQ.js b/assets/papers_2021_starr_greaney_a.md.D_r99KiD.js
similarity index 98%
rename from assets/papers_2021_starr_greaney_a.md.CXuiZgBQ.js
rename to assets/papers_2021_starr_greaney_a.md.D_r99KiD.js
index e7c3139..b3d650a 100644
--- a/assets/papers_2021_starr_greaney_a.md.CXuiZgBQ.js
+++ b/assets/papers_2021_starr_greaney_a.md.D_r99KiD.js
@@ -1 +1 @@
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-import{_ as n,c as t,o as a,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_gentles.html"}]]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),l=[r,s];function d(c,h,u,f,p,m){return a(),t("div",null,l)}const y=n(o,[["render",d]]);export{b as __pageData,y as default};
+import{_ as n,c as t,o as a,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_gentles.html"}]]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),l=[r,s];function d(c,h,u,f,p,m){return a(),t("div",null,l)}const y=n(o,[["render",d]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2022_gentles.md.CykcdMMz.lean.js b/assets/papers_2022_gentles.md.DyLaKwN-.lean.js
similarity index 97%
rename from assets/papers_2022_gentles.md.CykcdMMz.lean.js
rename to assets/papers_2022_gentles.md.DyLaKwN-.lean.js
index 627715c..b7f2d20 100644
--- a/assets/papers_2022_gentles.md.CykcdMMz.lean.js
+++ b/assets/papers_2022_gentles.md.DyLaKwN-.lean.js
@@ -1 +1 @@
-import{_ as n,c as t,o as a,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_gentles.html"}]]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),l=[r,s];function d(c,h,u,f,p,m){return a(),t("div",null,l)}const y=n(o,[["render",d]]);export{b as __pageData,y as default};
+import{_ as n,c as t,o as a,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","description":"","frontmatter":{"layout":"paper","title":"Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time","date":"2022-01-25","authors":["Lauren E Gentles","Leanne Kehoe","Katharine HD Crawford","Kirsten Lacombe","Jane Dickerson","Caitlin Wolf","Joanna Yuan","Susanna Schuler","John T Watson","Sankan Nyanseor","Melissa Briggs-Hagen","Sharon Saydah","Claire M Midgley","Kimberly Pringle","Helen Chu","Jesse D Bloom","Janet A Englund"],"journal":"medRxiv","doi":"10.1101/2022.01.14.22269235","link":"https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1","image":"/assets/papers/2022_gentles.jpg","keywords":["SARS-CoV-2","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_gentles.html"}]]},"headers":[],"relativePath":"papers/2022_gentles.md","filePath":"papers/2022_gentles.md"}'),o={name:"papers/2022_gentles.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.",-1),l=[r,s];function d(c,h,u,f,p,m){return a(),t("div",null,l)}const y=n(o,[["render",d]]);export{b as __pageData,y as default};
diff --git a/assets/papers_2022_greaney_a.md.Dqhb0fOm.js b/assets/papers_2022_greaney_a.md.CDNzafri.js
similarity index 97%
rename from assets/papers_2022_greaney_a.md.Dqhb0fOm.js
rename to assets/papers_2022_greaney_a.md.CDNzafri.js
index 487720b..3fe8b0e 100644
--- a/assets/papers_2022_greaney_a.md.Dqhb0fOm.js
+++ b/assets/papers_2022_greaney_a.md.CDNzafri.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default};
diff --git a/assets/papers_2022_greaney_a.md.Dqhb0fOm.lean.js b/assets/papers_2022_greaney_a.md.CDNzafri.lean.js
similarity index 97%
rename from assets/papers_2022_greaney_a.md.Dqhb0fOm.lean.js
rename to assets/papers_2022_greaney_a.md.CDNzafri.lean.js
index 487720b..3fe8b0e 100644
--- a/assets/papers_2022_greaney_a.md.Dqhb0fOm.lean.js
+++ b/assets/papers_2022_greaney_a.md.CDNzafri.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default};
+import{_ as a,c as t,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","description":"","frontmatter":{"layout":"paper","title":"The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes","date":"2022-06-29","authors":["Allison J Greaney","Rachel T Eguia","Tyler N Starr","Khadija Khan","Nicholas Franko","Jennifer K Logue","Sandra M Lord","Cate Speake","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS Pathogens","doi":"10.1371/journal.ppat.1010592","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592","image":"/assets/papers/2022_greaney_a.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_a.md","filePath":"papers/2022_greaney_a.md"}'),o={name:"papers/2022_greaney_a.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.",-1),l=[s,r];function c(d,p,h,u,y,g){return n(),t("div",null,l)}const m=a(o,[["render",c]]);export{f as __pageData,m as default};
diff --git a/assets/papers_2022_greaney_b.md.DrI6CCEC.js b/assets/papers_2022_greaney_b.md.DK5PFXVz.js
similarity index 97%
rename from assets/papers_2022_greaney_b.md.DrI6CCEC.js
rename to assets/papers_2022_greaney_b.md.DK5PFXVz.js
index 73688cd..2ecf69c 100644
--- a/assets/papers_2022_greaney_b.md.DrI6CCEC.js
+++ b/assets/papers_2022_greaney_b.md.DK5PFXVz.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,m,u,b){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,m,u,b){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2022_greaney_b.md.DrI6CCEC.lean.js b/assets/papers_2022_greaney_b.md.DK5PFXVz.lean.js
similarity index 97%
rename from assets/papers_2022_greaney_b.md.DrI6CCEC.lean.js
rename to assets/papers_2022_greaney_b.md.DK5PFXVz.lean.js
index 73688cd..2ecf69c 100644
--- a/assets/papers_2022_greaney_b.md.DrI6CCEC.lean.js
+++ b/assets/papers_2022_greaney_b.md.DK5PFXVz.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,m,u,b){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as a,c as t,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","description":"","frontmatter":{"layout":"paper","title":"A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy","date":"2022-02-08","authors":["Allison J Greaney","Tyler N Starr","Rachel T Eguia","Andrea N Loes","Khadija Khan","Farina Karim","Sandile Cele","John E Bowen","Jennifer K Logue","Davide Corti","David Veesler","Helen Y Chu","Alex Sigal","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010248","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248","image":"/assets/papers/2022_greaney_b.png","keywords":["SARS-CoV-2","Deep mutational scanning","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_b.md","filePath":"papers/2022_greaney_b.md"}'),s={name:"papers/2022_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",-1),l=[o,r];function c(d,h,p,m,u,b){return i(),t("div",null,l)}const _=a(s,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2022_greaney_c.md.CI19aPFQ.js b/assets/papers_2022_greaney_c.md.Dkb2jTG4.js
similarity index 97%
rename from assets/papers_2022_greaney_c.md.CI19aPFQ.js
rename to assets/papers_2022_greaney_c.md.Dkb2jTG4.js
index 5037b72..9674c44 100644
--- a/assets/papers_2022_greaney_c.md.CI19aPFQ.js
+++ b/assets/papers_2022_greaney_c.md.Dkb2jTG4.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[a("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),a(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,_){return i(),o("div",null,c)}const y=t(r,[["render",l]]);export{f as __pageData,y as default};
+import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[a("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),a(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,_){return i(),o("div",null,c)}const y=t(r,[["render",l]]);export{f as __pageData,y as default};
diff --git a/assets/papers_2022_greaney_c.md.CI19aPFQ.lean.js b/assets/papers_2022_greaney_c.md.Dkb2jTG4.lean.js
similarity index 97%
rename from assets/papers_2022_greaney_c.md.CI19aPFQ.lean.js
rename to assets/papers_2022_greaney_c.md.Dkb2jTG4.lean.js
index 5037b72..9674c44 100644
--- a/assets/papers_2022_greaney_c.md.CI19aPFQ.lean.js
+++ b/assets/papers_2022_greaney_c.md.Dkb2jTG4.lean.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[a("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),a(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,_){return i(),o("div",null,c)}const y=t(r,[["render",l]]);export{f as __pageData,y as default};
+import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","description":"","frontmatter":{"layout":"paper","title":"An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain","date":"2022-01-01","authors":["Allison J Greaney","Tyler N Starr","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac021","link":"https://academic.oup.com/ve/article/8/1/veac021/6549895","image":"/assets/papers/2022_greaney_c.jpg","keywords":["SARS-CoV-2","Software tools","Immunity"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_greaney_c.html"}]]},"headers":[],"relativePath":"papers/2022_greaney_c.md","filePath":"papers/2022_greaney_c.md"}'),r={name:"papers/2022_greaney_c.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,[a("A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at "),e("a",{href:"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/"),a(" (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.")],-1),c=[n,s];function l(d,p,m,h,u,_){return i(),o("div",null,c)}const y=t(r,[["render",l]]);export{f as __pageData,y as default};
diff --git a/assets/papers_2022_hannon.md.XhxghO_4.js b/assets/papers_2022_hannon.md.BAvYNPLo.js
similarity index 97%
rename from assets/papers_2022_hannon.md.XhxghO_4.js
rename to assets/papers_2022_hannon.md.BAvYNPLo.js
index 54ba6e8..6919c72 100644
--- a/assets/papers_2022_hannon.md.XhxghO_4.js
+++ b/assets/papers_2022_hannon.md.BAvYNPLo.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_hannon.html"}]]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),l=[r,s];function d(c,h,u,m,v,p){return i(),a("div",null,l)}const b=t(o,[["render",d]]);export{g as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_hannon.html"}]]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),l=[r,s];function d(c,h,u,m,v,p){return i(),a("div",null,l)}const b=t(o,[["render",d]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2022_hannon.md.XhxghO_4.lean.js b/assets/papers_2022_hannon.md.BAvYNPLo.lean.js
similarity index 97%
rename from assets/papers_2022_hannon.md.XhxghO_4.lean.js
rename to assets/papers_2022_hannon.md.BAvYNPLo.lean.js
index 54ba6e8..6919c72 100644
--- a/assets/papers_2022_hannon.md.XhxghO_4.lean.js
+++ b/assets/papers_2022_hannon.md.BAvYNPLo.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_hannon.html"}]]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),l=[r,s];function d(c,h,u,m,v,p){return i(),a("div",null,l)}const b=t(o,[["render",d]]);export{g as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","description":"","frontmatter":{"layout":"paper","title":"Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat","date":"2022-07-01","authors":["William W Hannon","Pavitra Roychoudhury","Hong Xie","Lasata Shrestha","Amin Addetia","Keith R Jerome","Alexander L Greninger","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac052","link":"https://academic.oup.com/ve/article/8/2/veac052/6609212","image":"/assets/papers/2022_hannon.jpg","keywords":["SARS-CoV-2","Within-host evolution"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_hannon.html"}]]},"headers":[],"relativePath":"papers/2022_hannon.md","filePath":"papers/2022_hannon.md"}'),o={name:"papers/2022_hannon.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.",-1),l=[r,s];function d(c,h,u,m,v,p){return i(),a("div",null,l)}const b=t(o,[["render",d]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2022_starr_a.md.Dh9CDVqf.js b/assets/papers_2022_starr_a.md.Btv9VMRR.js
similarity index 97%
rename from assets/papers_2022_starr_a.md.Dh9CDVqf.js
rename to assets/papers_2022_starr_a.md.Btv9VMRR.js
index c75253b..e564806 100644
--- a/assets/papers_2022_starr_a.md.Dh9CDVqf.js
+++ b/assets/papers_2022_starr_a.md.Btv9VMRR.js
@@ -1 +1 @@
-import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),l=[n,i];function d(c,h,b,u,p,v){return t(),s("div",null,l)}const m=a(o,[["render",d]]);export{g as __pageData,m as default};
+import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),l=[n,i];function d(c,h,b,u,p,v){return t(),s("div",null,l)}const m=a(o,[["render",d]]);export{g as __pageData,m as default};
diff --git a/assets/papers_2022_starr_a.md.Dh9CDVqf.lean.js b/assets/papers_2022_starr_a.md.Btv9VMRR.lean.js
similarity index 97%
rename from assets/papers_2022_starr_a.md.Dh9CDVqf.lean.js
rename to assets/papers_2022_starr_a.md.Btv9VMRR.lean.js
index c75253b..e564806 100644
--- a/assets/papers_2022_starr_a.md.Dh9CDVqf.lean.js
+++ b/assets/papers_2022_starr_a.md.Btv9VMRR.lean.js
@@ -1 +1 @@
-import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),l=[n,i];function d(c,h,b,u,p,v){return t(),s("div",null,l)}const m=a(o,[["render",d]]);export{g as __pageData,m as default};
+import{_ as a,c as s,o as t,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","description":"","frontmatter":{"layout":"paper","title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","date":"2022-03-31","authors":["Tyler N Starr","Samantha K Zepeda","Alexandra C Walls","Allison J Greaney","Sergey Alkhovsky","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-022-04464-z","link":"https://www.nature.com/articles/s41586-022-04464-z","image":"/assets/papers/2022_starr_a.jpg","keywords":["Coronavirus","Phylogenetics","Yeast display"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_a.md","filePath":"papers/2022_starr_a.md"}'),o={name:"papers/2022_starr_a.md"},n=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.",-1),l=[n,i];function d(c,h,b,u,p,v){return t(),s("div",null,l)}const m=a(o,[["render",d]]);export{g as __pageData,m as default};
diff --git a/assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.js b/assets/papers_2022_starr_greaney_a.md.C7LW8FTl.js
similarity index 98%
rename from assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.js
rename to assets/papers_2022_starr_greaney_a.md.C7LW8FTl.js
index 2d30a6c..bc9442e 100644
--- a/assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.js
+++ b/assets/papers_2022_starr_greaney_a.md.C7LW8FTl.js
@@ -1 +1 @@
-import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default};
+import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.lean.js b/assets/papers_2022_starr_greaney_a.md.C7LW8FTl.lean.js
similarity index 98%
rename from assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.lean.js
rename to assets/papers_2022_starr_greaney_a.md.C7LW8FTl.lean.js
index 2d30a6c..bc9442e 100644
--- a/assets/papers_2022_starr_greaney_a.md.SX4ri2Hz.lean.js
+++ b/assets/papers_2022_starr_greaney_a.md.C7LW8FTl.lean.js
@@ -1 +1 @@
-import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default};
+import{_ as a,c as n,o as t,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains","date":"2022-11-18","authors":["Tyler N Starr*","Allison J Greaney*","Cameron M Stewart","Alexandra C Walls","William W Hannon","David Veesler","Jesse D Bloom"],"journal":"PLoS pathogens","doi":"10.1371/journal.ppat.1010951","link":"https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951","image":"/assets/papers/2022_starr_greaney_a.png","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_a.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_a.md","filePath":"papers/2022_starr_greaney_a.md"}'),s={name:"papers/2022_starr_greaney_a.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.",-1),c=[o,r];function d(l,h,p,m,u,f){return t(),n("div",null,c)}const _=a(s,[["render",d]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2022_starr_greaney_b.md.xiiYgZfH.js b/assets/papers_2022_starr_greaney_b.md.fVTUz0TI.js
similarity index 97%
rename from assets/papers_2022_starr_greaney_b.md.xiiYgZfH.js
rename to assets/papers_2022_starr_greaney_b.md.fVTUz0TI.js
index 6e62b20..5b224ca 100644
--- a/assets/papers_2022_starr_greaney_b.md.xiiYgZfH.js
+++ b/assets/papers_2022_starr_greaney_b.md.fVTUz0TI.js
@@ -1 +1 @@
-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2022_starr_greaney_b.md.xiiYgZfH.lean.js b/assets/papers_2022_starr_greaney_b.md.fVTUz0TI.lean.js
similarity index 97%
rename from assets/papers_2022_starr_greaney_b.md.xiiYgZfH.lean.js
rename to assets/papers_2022_starr_greaney_b.md.fVTUz0TI.lean.js
index 6e62b20..5b224ca 100644
--- a/assets/papers_2022_starr_greaney_b.md.xiiYgZfH.lean.js
+++ b/assets/papers_2022_starr_greaney_b.md.fVTUz0TI.lean.js
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-import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default};
+import{_ as t,c as a,o as i,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","description":"","frontmatter":{"layout":"paper","title":"Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution","date":"2022-07-22","authors":["Tyler N Starr*","Allison J Greaney*","William W Hannon","Andrea N Loes","Kevin Hauser","Josh R Dillen","Elena Ferri","Ariana Ghez Farrell","Bernadeta Dadonaite","Matthew McCallum","Kenneth A Matreyek","Davide Corti","David Veesler","Gyorgy Snell","Jesse D Bloom"],"journal":"Science","doi":"10.1126/science.abo7896","link":"https://www.science.org/doi/full/10.1126/science.abo7896","image":"/assets/papers/2022_starr_greaney_b.jpg","keywords":["SARS-CoV-2","Yeast display","Deep mutational scanning","Epistasis"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_starr_greaney_b.html"}]]},"headers":[],"relativePath":"papers/2022_starr_greaney_b.md","filePath":"papers/2022_starr_greaney_b.md"}'),s={name:"papers/2022_starr_greaney_b.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.",-1),l=[o,r];function c(h,d,p,u,m,f){return i(),a("div",null,l)}const b=t(s,[["render",c]]);export{g as __pageData,b as default};
diff --git a/assets/papers_2022_yu.md.CFrff2Ef.js b/assets/papers_2022_yu.md.BCuqOyPs.js
similarity index 96%
rename from assets/papers_2022_yu.md.CFrff2Ef.js
rename to assets/papers_2022_yu.md.BCuqOyPs.js
index 8bc4a66..0a2e1de 100644
--- a/assets/papers_2022_yu.md.CFrff2Ef.js
+++ b/assets/papers_2022_yu.md.BCuqOyPs.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_yu.html"}]]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_yu.html"}]]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2022_yu.md.CFrff2Ef.lean.js b/assets/papers_2022_yu.md.BCuqOyPs.lean.js
similarity index 96%
rename from assets/papers_2022_yu.md.CFrff2Ef.lean.js
rename to assets/papers_2022_yu.md.BCuqOyPs.lean.js
index 8bc4a66..0a2e1de 100644
--- a/assets/papers_2022_yu.md.CFrff2Ef.lean.js
+++ b/assets/papers_2022_yu.md.BCuqOyPs.lean.js
@@ -1 +1 @@
-import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_yu.html"}]]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default};
+import{_ as t,c as o,o as i,b as e,d as a}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"A biophysical model of viral escape from polyclonal antibodies","description":"","frontmatter":{"layout":"paper","title":"A biophysical model of viral escape from polyclonal antibodies","date":"2022-07-01","authors":["Timothy C Yu","Zorian T Thornton","William W Hannon","William S DeWitt","Caelan E Radford","Frederick A Matsen IV","Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/veac110","link":"https://academic.oup.com/ve/article/8/2/veac110/6889254","image":"/assets/papers/2022_yu.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2022_yu.html"}]]},"headers":[],"relativePath":"papers/2022_yu.md","filePath":"papers/2022_yu.md"}'),n={name:"papers/2022_yu.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),l=e("p",null,[a("A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at "),e("a",{href:"https://jbloomlab.github.io/polyclonal",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/polyclonal"),a(".")],-1),r=[s,l];function c(p,d,h,m,u,b){return i(),o("div",null,r)}const _=t(n,[["render",c]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2023_bacsik.md.Cw8R980L.js b/assets/papers_2023_bacsik.md.BYXMAgFl.js
similarity index 97%
rename from assets/papers_2023_bacsik.md.Cw8R980L.js
rename to assets/papers_2023_bacsik.md.BYXMAgFl.js
index 1fc0273..e5a54d7 100644
--- a/assets/papers_2023_bacsik.md.Cw8R980L.js
+++ b/assets/papers_2023_bacsik.md.BYXMAgFl.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bacsik.html"}]]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return n(),a("div",null,l)}const y=t(o,[["render",c]]);export{g as __pageData,y as default};
+import{_ as t,c as a,o as n,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bacsik.html"}]]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return n(),a("div",null,l)}const y=t(o,[["render",c]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2023_bacsik.md.Cw8R980L.lean.js b/assets/papers_2023_bacsik.md.BYXMAgFl.lean.js
similarity index 97%
rename from assets/papers_2023_bacsik.md.Cw8R980L.lean.js
rename to assets/papers_2023_bacsik.md.BYXMAgFl.lean.js
index 1fc0273..e5a54d7 100644
--- a/assets/papers_2023_bacsik.md.Cw8R980L.lean.js
+++ b/assets/papers_2023_bacsik.md.BYXMAgFl.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as r}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bacsik.html"}]]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return n(),a("div",null,l)}const y=t(o,[["render",c]]);export{g as __pageData,y as default};
+import{_ as t,c as a,o as n,b as e,d as r}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Influenza virus transcription and progeny production are poorly correlated in single cells","description":"","frontmatter":{"layout":"paper","title":"Influenza virus transcription and progeny production are poorly correlated in single cells","date":"2023-09-07","authors":["David J Bacsik","Bernadeta Dadonaite","Andrew Butler","Allison J Greaney","Nicholas S Heaton","Jesse D Bloom"],"journal":"eLife","doi":"10.7554/eLife.86852.2","link":"https://elifesciences.org/articles/86852","image":"/assets/papers/2023_bacsik.jpg","selected":true,"keywords":["Single-cell sequencing","Influenza"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bacsik.html"}]]},"headers":[],"relativePath":"papers/2023_bacsik.md","filePath":"papers/2023_bacsik.md"}'),o={name:"papers/2023_bacsik.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[r("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.",-1),l=[i,s];function c(d,p,u,f,h,m){return n(),a("div",null,l)}const y=t(o,[["render",c]]);export{g as __pageData,y as default};
diff --git a/assets/papers_2023_bloom_a.md.BdUV1xMh.js b/assets/papers_2023_bloom_a.md.D1yNwSui.js
similarity index 96%
rename from assets/papers_2023_bloom_a.md.BdUV1xMh.js
rename to assets/papers_2023_bloom_a.md.D1yNwSui.js
index b9ff698..d2f530a 100644
--- a/assets/papers_2023_bloom_a.md.BdUV1xMh.js
+++ b/assets/papers_2023_bloom_a.md.D1yNwSui.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const S=a(n,[["render",m]]);export{y as __pageData,S as default};
+import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const S=a(n,[["render",m]]);export{y as __pageData,S as default};
diff --git a/assets/papers_2023_bloom_a.md.BdUV1xMh.lean.js b/assets/papers_2023_bloom_a.md.D1yNwSui.lean.js
similarity index 96%
rename from assets/papers_2023_bloom_a.md.BdUV1xMh.lean.js
rename to assets/papers_2023_bloom_a.md.D1yNwSui.lean.js
index b9ff698..d2f530a 100644
--- a/assets/papers_2023_bloom_a.md.BdUV1xMh.lean.js
+++ b/assets/papers_2023_bloom_a.md.D1yNwSui.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const y=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const S=a(n,[["render",m]]);export{y as __pageData,S as default};
+import{_ as a,c as t,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const y=JSON.parse('{"title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market","date":"2023-07-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead050","link":"https://academic.oup.com/ve/article/9/2/vead050/7249794","image":"/assets/papers/2023_bloom_a.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_a.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_a.md","filePath":"papers/2023_bloom_a.md"}'),n={name:"papers/2023_bloom_a.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.",-1),l=[r,i];function m(c,d,h,p,f,u){return o(),t("div",null,l)}const S=a(n,[["render",m]]);export{y as __pageData,S as default};
diff --git a/assets/papers_2023_bloom_b.md.BpPBCe13.js b/assets/papers_2023_bloom_b.md.BawhRDJ5.js
similarity index 95%
rename from assets/papers_2023_bloom_b.md.BpPBCe13.js
rename to assets/papers_2023_bloom_b.md.BawhRDJ5.js
index 6675b36..efbe16f 100644
--- a/assets/papers_2023_bloom_b.md.BpPBCe13.js
+++ b/assets/papers_2023_bloom_b.md.BawhRDJ5.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2023_bloom_b.md.BpPBCe13.lean.js b/assets/papers_2023_bloom_b.md.BawhRDJ5.lean.js
similarity index 95%
rename from assets/papers_2023_bloom_b.md.BpPBCe13.lean.js
rename to assets/papers_2023_bloom_b.md.BawhRDJ5.lean.js
index 6675b36..efbe16f 100644
--- a/assets/papers_2023_bloom_b.md.BpPBCe13.lean.js
+++ b/assets/papers_2023_bloom_b.md.BawhRDJ5.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{g as __pageData,_ as default};
+import{_ as t,c as a,o,b as e,d as s}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Evolution of the SARS-CoV-2 mutational spectrum","description":"","frontmatter":{"layout":"paper","title":"Evolution of the SARS-CoV-2 mutational spectrum","date":"2023-04-11","authors":["Jesse D Bloom","Annabel C Beichman","Richard A Neher","Kelley Harris"],"journal":"Molecular Biology and Evolution","doi":"10.1093/molbev/msad085","link":"https://academic.oup.com/mbe/article/40/4/msad085/7113660","image":"/assets/papers/2023_bloom_b.jpg","keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_b.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_b.md","filePath":"papers/2023_bloom_b.md"}'),i={name:"papers/2023_bloom_b.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[s("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),n=e("p",null,"SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.",-1),l=[r,n];function c(h,m,u,d,p,f){return o(),a("div",null,l)}const _=t(i,[["render",c]]);export{g as __pageData,_ as default};
diff --git a/assets/papers_2023_bloom_c.md.CwM1hAHW.js b/assets/papers_2023_bloom_c.md.C8sP_775.js
similarity index 97%
rename from assets/papers_2023_bloom_c.md.CwM1hAHW.js
rename to assets/papers_2023_bloom_c.md.C8sP_775.js
index fb10bb0..3c32b1e 100644
--- a/assets/papers_2023_bloom_c.md.CwM1hAHW.js
+++ b/assets/papers_2023_bloom_c.md.C8sP_775.js
@@ -1 +1 @@
-import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_c.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[r,i];function l(m,p,f,d,h,u){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default};
+import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_c.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[r,i];function l(m,p,f,d,h,u){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2023_bloom_c.md.CwM1hAHW.lean.js b/assets/papers_2023_bloom_c.md.C8sP_775.lean.js
similarity index 97%
rename from assets/papers_2023_bloom_c.md.CwM1hAHW.lean.js
rename to assets/papers_2023_bloom_c.md.C8sP_775.lean.js
index fb10bb0..3c32b1e 100644
--- a/assets/papers_2023_bloom_c.md.CwM1hAHW.lean.js
+++ b/assets/papers_2023_bloom_c.md.C8sP_775.lean.js
@@ -1 +1 @@
-import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_c.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[r,i];function l(m,p,f,d,h,u){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default};
+import{_ as o,c as a,o as s,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Fitness effects of mutations to SARS-CoV-2 proteins","description":"","frontmatter":{"layout":"paper","title":"Fitness effects of mutations to SARS-CoV-2 proteins","date":"2023-09-18","authors":["Jesse D Bloom","Richard A Neher"],"journal":"Virus Evolution","doi":"10.1093/ve/veae026","link":"https://academic.oup.com/ve/article/9/2/vead055/7265011","image":"/assets/papers/2023_bloom_c.jpg","selected":true,"keywords":["SARS-CoV-2","Phylogenetics"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_bloom_c.html"}]]},"headers":[],"relativePath":"papers/2023_bloom_c.md","filePath":"papers/2023_bloom_c.md"}'),n={name:"papers/2023_bloom_c.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,[t("Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins ("),e("a",{href:"https://jbloomlab.github.io/SARS2-mut-fitness/",target:"_blank",rel:"noreferrer"},"https://jbloomlab.github.io/SARS2-mut-fitness/"),t("). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.")],-1),c=[r,i];function l(m,p,f,d,h,u){return s(),a("div",null,c)}const v=o(n,[["render",l]]);export{_ as __pageData,v as default};
diff --git a/assets/papers_2023_dadonaite_crawford_radford.md.Dajg5mU6.js b/assets/papers_2023_dadonaite_crawford_radford.md.DUnzKTfF.js
similarity index 97%
rename from assets/papers_2023_dadonaite_crawford_radford.md.Dajg5mU6.js
rename to assets/papers_2023_dadonaite_crawford_radford.md.DUnzKTfF.js
index edb6148..3a8615d 100644
--- a/assets/papers_2023_dadonaite_crawford_radford.md.Dajg5mU6.js
+++ b/assets/papers_2023_dadonaite_crawford_radford.md.DUnzKTfF.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_dadonaite_crawford_radford.html"}]]},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),i={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(i,[["render",l]]);export{b as __pageData,g as default};
+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_dadonaite_crawford_radford.html"}]]},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),i={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(i,[["render",l]]);export{b as __pageData,g as default};
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similarity index 97%
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index edb6148..3a8615d 100644
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-import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_dadonaite_crawford_radford.html"}]]},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),i={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(i,[["render",l]]);export{b as __pageData,g as default};
+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","description":"","frontmatter":{"layout":"paper","title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","date":"2023-03-16","authors":["Bernadeta Dadonaite*","Katharine HD Crawford*","Caelan E Radford*","Ariana G Farrell","C Yu Timothy","William W Hannon","Panpan Zhou","Raiees Andrabi","Dennis R Burton","Lihong Liu","David D Ho","Helen Y Chu","Richard A Neher","Jesse D Bloom"],"journal":"Cell","doi":"10.1016/j.cell.2023.02.001","link":"https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf","image":"/assets/papers/2023_dadonaite_crawford_radford.png","keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_dadonaite_crawford_radford.html"}]]},"headers":[],"relativePath":"papers/2023_dadonaite_crawford_radford.md","filePath":"papers/2023_dadonaite_crawford_radford.md"}'),i={name:"papers/2023_dadonaite_crawford_radford.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),s=e("p",null,"A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.",-1),d=[r,s];function l(c,p,u,f,h,m){return n(),t("div",null,d)}const g=a(i,[["render",l]]);export{b as __pageData,g as default};
diff --git a/assets/papers_2023_kikawa.md.CvVV_BpW.js b/assets/papers_2023_kikawa.md.C3vGnjgP.js
similarity index 97%
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index 10272cb..fe45f3c 100644
--- a/assets/papers_2023_kikawa.md.CvVV_BpW.js
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-import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_kikawa.html"}]]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,p,u,f,h,b){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{g as __pageData,v as default};
+import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_kikawa.html"}]]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,p,u,f,h,b){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2023_kikawa.md.CvVV_BpW.lean.js b/assets/papers_2023_kikawa.md.C3vGnjgP.lean.js
similarity index 97%
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rename to assets/papers_2023_kikawa.md.C3vGnjgP.lean.js
index 10272cb..fe45f3c 100644
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+++ b/assets/papers_2023_kikawa.md.C3vGnjgP.lean.js
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-import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_kikawa.html"}]]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,p,u,f,h,b){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{g as __pageData,v as default};
+import{_ as a,c as i,o as t,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","description":"","frontmatter":{"layout":"paper","title":"The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies","date":"2023-11-30","authors":["Caroline Kikawa","Catiana H Cartwright-Acar","Jackson B Stuart","Maya Contreras","Lisa M Levoir","Matthew J Evans","Jesse D Bloom","Leslie Goo"],"journal":"Journal of Virology","doi":"10.1128/jvi.01414-23","link":"https://journals.asm.org/doi/full/10.1128/jvi.01414-23","image":"/assets/papers/2023_kikawa.jpg","keywords":["Zika","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_kikawa.html"}]]},"headers":[],"relativePath":"papers/2023_kikawa.md","filePath":"papers/2023_kikawa.md"}'),o={name:"papers/2023_kikawa.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.",-1),l=[s,r];function c(d,p,u,f,h,b){return t(),i("div",null,l)}const v=a(o,[["render",c]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2023_radford.md.yr7KJDOP.js b/assets/papers_2023_radford.md.Wvx-gaY_.js
similarity index 97%
rename from assets/papers_2023_radford.md.yr7KJDOP.js
rename to assets/papers_2023_radford.md.Wvx-gaY_.js
index 03bf5fa..f6673b5 100644
--- a/assets/papers_2023_radford.md.yr7KJDOP.js
+++ b/assets/papers_2023_radford.md.Wvx-gaY_.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_radford.html"}]]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),o={name:"papers/2023_radford.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),l=[s,r];function c(d,p,m,h,u,f){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_radford.html"}]]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),o={name:"papers/2023_radford.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),l=[s,r];function c(d,p,m,h,u,f){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2023_radford.md.yr7KJDOP.lean.js b/assets/papers_2023_radford.md.Wvx-gaY_.lean.js
similarity index 97%
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rename to assets/papers_2023_radford.md.Wvx-gaY_.lean.js
index 03bf5fa..f6673b5 100644
--- a/assets/papers_2023_radford.md.yr7KJDOP.lean.js
+++ b/assets/papers_2023_radford.md.Wvx-gaY_.lean.js
@@ -1 +1 @@
-import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_radford.html"}]]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),o={name:"papers/2023_radford.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),l=[s,r];function c(d,p,m,h,u,f){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
+import{_ as t,c as a,o as n,b as e,d as i}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","description":"","frontmatter":{"layout":"paper","title":"Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning","date":"2023-07-12","authors":["Caelan E Radford","Philipp Schommers","Lutz Gieselmann","Katharine HD Crawford","Bernadeta Dadonaite","Timothy C Yu","Adam S Dingens","Julie Overbaugh","Florian Klein","Jesse D Bloom"],"journal":"Cell Host & Microbe","doi":"10.1016/j.chom.2023.05.025","link":"https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf","image":"/assets/papers/2023_radford.png","keywords":["HIV","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2023_radford.html"}]]},"headers":[],"relativePath":"papers/2023_radford.md","filePath":"papers/2023_radford.md"}'),o={name:"papers/2023_radford.md"},s=e("h2",{id:"abstract",tabindex:"-1"},[i("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.",-1),l=[s,r];function c(d,p,m,h,u,f){return n(),a("div",null,l)}const _=t(o,[["render",c]]);export{b as __pageData,_ as default};
diff --git a/assets/papers_2024_bloom.md.DgjCzQH_.js b/assets/papers_2024_bloom.md.DovSGDEc.js
similarity index 96%
rename from assets/papers_2024_bloom.md.DgjCzQH_.js
rename to assets/papers_2024_bloom.md.DovSGDEc.js
index 19040b8..2819772 100644
--- a/assets/papers_2024_bloom.md.DgjCzQH_.js
+++ b/assets/papers_2024_bloom.md.DovSGDEc.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_bloom.html"}]]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return o(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default};
+import{_ as a,c as t,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_bloom.html"}]]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return o(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2024_bloom.md.DgjCzQH_.lean.js b/assets/papers_2024_bloom.md.DovSGDEc.lean.js
similarity index 96%
rename from assets/papers_2024_bloom.md.DgjCzQH_.lean.js
rename to assets/papers_2024_bloom.md.DovSGDEc.lean.js
index 19040b8..2819772 100644
--- a/assets/papers_2024_bloom.md.DgjCzQH_.lean.js
+++ b/assets/papers_2024_bloom.md.DovSGDEc.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o,b as e,d as n}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_bloom.html"}]]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return o(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default};
+import{_ as a,c as t,o,b as e,d as n}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","description":"","frontmatter":{"layout":"paper","title":"Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market","date":"2024-01-01","authors":["Jesse D Bloom"],"journal":"Virus Evolution","doi":"10.1093/ve/vead089","link":"https://academic.oup.com/ve/article/10/1/vead089/7504441","image":"/assets/papers/2024_bloom.jpg","keywords":["SARS-CoV-2"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_bloom.html"}]]},"headers":[],"relativePath":"papers/2024_bloom.md","filePath":"papers/2024_bloom.md"}'),s={name:"papers/2024_bloom.md"},r=e("h2",{id:"abstract",tabindex:"-1"},[n("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),i=e("p",null,"In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.",-1),l=[r,i];function m(h,c,d,f,u,p){return o(),t("div",null,l)}const v=a(s,[["render",m]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2024_carr.md.C_k67N-5.js b/assets/papers_2024_carr.md.BJ641qhK.js
similarity index 95%
rename from assets/papers_2024_carr.md.C_k67N-5.js
rename to assets/papers_2024_carr.md.BJ641qhK.js
index 53acc01..ea35786 100644
--- a/assets/papers_2024_carr.md.C_k67N-5.js
+++ b/assets/papers_2024_carr.md.BJ641qhK.js
@@ -1 +1 @@
-import{_ as a,c as e,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_carr.html"}]]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/LASV_Josiah_GP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/LASV_Josiah_GP_DMS/</a></p>',4),r=[o];function n(l,c,u,d,p,h){return t(),e("div",null,r)}const f=a(s,[["render",n]]);export{_ as __pageData,f as default};
+import{_ as a,c as e,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_carr.html"}]]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/LASV_Josiah_GP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/LASV_Josiah_GP_DMS/</a></p>',4),r=[o];function n(l,c,u,d,p,h){return t(),e("div",null,r)}const f=a(s,[["render",n]]);export{_ as __pageData,f as default};
diff --git a/assets/papers_2024_carr.md.C_k67N-5.lean.js b/assets/papers_2024_carr.md.BJ641qhK.lean.js
similarity index 89%
rename from assets/papers_2024_carr.md.C_k67N-5.lean.js
rename to assets/papers_2024_carr.md.BJ641qhK.lean.js
index 085398f..dff8c89 100644
--- a/assets/papers_2024_carr.md.C_k67N-5.lean.js
+++ b/assets/papers_2024_carr.md.BJ641qhK.lean.js
@@ -1 +1 @@
-import{_ as a,c as e,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_carr.html"}]]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i("",4),r=[o];function n(l,c,u,d,p,h){return t(),e("div",null,r)}const f=a(s,[["render",n]]);export{_ as __pageData,f as default};
+import{_ as a,c as e,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex","date":"2024-07-15","authors":["Caleb R Carr*","Katharine HD Crawford*","Michael Murphy","Jared G Galloway","Hugh K Haddox","Frederick A Matsen","Kristian G Andersen","Neil P King","Jesse D Bloom"],"journal":"Immunity","doi":"10.1016/j.immuni.2024.06.013","link":"https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4","image":"/assets/papers/2024_carr.jpg","selected":true,"keywords":["Lassa","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_carr.html"}]]},"headers":[],"relativePath":"papers/2024_carr.md","filePath":"papers/2024_carr.md"}'),s={name:"papers/2024_carr.md"},o=i("",4),r=[o];function n(l,c,u,d,p,h){return t(),e("div",null,r)}const f=a(s,[["render",n]]);export{_ as __pageData,f as default};
diff --git a/assets/papers_2024_dadonaite_a.md.BK58CEDh.js b/assets/papers_2024_dadonaite_a.md.C2KGYYzB.js
similarity index 97%
rename from assets/papers_2024_dadonaite_a.md.BK58CEDh.js
rename to assets/papers_2024_dadonaite_a.md.C2KGYYzB.js
index 99b888f..3eb10e1 100644
--- a/assets/papers_2024_dadonaite_a.md.BK58CEDh.js
+++ b/assets/papers_2024_dadonaite_a.md.C2KGYYzB.js
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-import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_a.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function l(c,u,p,h,m,f){return n(),t("div",null,d)}const b=a(s,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_a.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function l(c,u,p,h,m,f){return n(),t("div",null,d)}const b=a(s,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2024_dadonaite_a.md.BK58CEDh.lean.js b/assets/papers_2024_dadonaite_a.md.C2KGYYzB.lean.js
similarity index 97%
rename from assets/papers_2024_dadonaite_a.md.BK58CEDh.lean.js
rename to assets/papers_2024_dadonaite_a.md.C2KGYYzB.lean.js
index 99b888f..3eb10e1 100644
--- a/assets/papers_2024_dadonaite_a.md.BK58CEDh.lean.js
+++ b/assets/papers_2024_dadonaite_a.md.C2KGYYzB.lean.js
@@ -1 +1 @@
-import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_a.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function l(c,u,p,h,m,f){return n(),t("div",null,d)}const b=a(s,[["render",l]]);export{_ as __pageData,b as default};
+import{_ as a,c as t,o as n,b as e,d as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","description":"","frontmatter":{"layout":"paper","title":"Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades","date":"2024-07-03","authors":["Bernadeta Dadonaite","Jack Brown","Teagan E McMahon","Ariana G Farrell","Marlin D Figgins","Daniel Asarnow","Cameron Stewart","Jimin Lee","Jenni Logue","Trevor Bedford","Ben Murrell","Helen Y Chu","David Veesler","Jesse D Bloom"],"journal":"Nature","doi":"10.1038/s41586-024-07636-1","link":"https://www.nature.com/articles/s41586-024-07636-1","image":"/assets/papers/2024_dadonaite_a.jpg","selected":true,"keywords":["SARS-CoV-2","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_a.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_a.md","filePath":"papers/2024_dadonaite_a.md"}'),s={name:"papers/2024_dadonaite_a.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[o("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how >9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.",-1),d=[i,r];function l(c,u,p,h,m,f){return n(),t("div",null,d)}const b=a(s,[["render",l]]);export{_ as __pageData,b as default};
diff --git a/assets/papers_2024_dadonaite_b.md.BORheFEr.js b/assets/papers_2024_dadonaite_b.md.2F6PWzwD.js
similarity index 96%
rename from assets/papers_2024_dadonaite_b.md.BORheFEr.js
rename to assets/papers_2024_dadonaite_b.md.2F6PWzwD.js
index 3aadf5e..d48e2c9 100644
--- a/assets/papers_2024_dadonaite_b.md.BORheFEr.js
+++ b/assets/papers_2024_dadonaite_b.md.2F6PWzwD.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_b.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},o=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the &gt;10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p>',4),s=[o];function r(l,c,d,u,h,m){return t(),a("div",null,s)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default};
+import{_ as e,c as a,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_b.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},o=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the &gt;10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p>',4),s=[o];function r(l,c,d,u,h,m){return t(),a("div",null,s)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2024_dadonaite_b.md.BORheFEr.lean.js b/assets/papers_2024_dadonaite_b.md.2F6PWzwD.lean.js
similarity index 89%
rename from assets/papers_2024_dadonaite_b.md.BORheFEr.lean.js
rename to assets/papers_2024_dadonaite_b.md.2F6PWzwD.lean.js
index 8343ad6..1672c0a 100644
--- a/assets/papers_2024_dadonaite_b.md.BORheFEr.lean.js
+++ b/assets/papers_2024_dadonaite_b.md.2F6PWzwD.lean.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_b.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},o=i("",4),s=[o];function r(l,c,d,u,h,m){return t(),a("div",null,s)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default};
+import{_ as e,c as a,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","description":"","frontmatter":{"layout":"paper","title":"Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance","date":"2024-05-23","authors":["Bernadeta Dadonaite","Jenny J Ahn","Jordan T Ort","Jin Yu","Colleen Furey","Annie Dosey","William W Hannon","Amy Vincent Baker","Richard J Webby","Neil P King","Yan Liu","Scott E Hensley","Thomas P Peacock","Louise H Moncla","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.05.23.595634","link":"https://doi.org/10.1101/2024.05.23.595634","image":"/assets/papers/2024_dadonaite_b.png","selected":true,"keywords":["Influenza","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_dadonaite_b.html"}]]},"headers":[],"relativePath":"papers/2024_dadonaite_b.md","filePath":"papers/2024_dadonaite_b.md"}'),n={name:"papers/2024_dadonaite_b.md"},o=i("",4),s=[o];function r(l,c,d,u,h,m){return t(),a("div",null,s)}const _=e(n,[["render",r]]);export{f as __pageData,_ as default};
diff --git a/assets/papers_2024_hannon.md.Yb1uIpIV.js b/assets/papers_2024_hannon.md.H8YxJdJi.js
similarity index 97%
rename from assets/papers_2024_hannon.md.Yb1uIpIV.js
rename to assets/papers_2024_hannon.md.H8YxJdJi.js
index f62c459..86893b5 100644
--- a/assets/papers_2024_hannon.md.Yb1uIpIV.js
+++ b/assets/papers_2024_hannon.md.H8YxJdJi.js
@@ -1 +1 @@
-import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_hannon.html"}]]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function l(u,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",l]]);export{g as __pageData,v as default};
+import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_hannon.html"}]]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function l(u,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",l]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2024_hannon.md.Yb1uIpIV.lean.js b/assets/papers_2024_hannon.md.H8YxJdJi.lean.js
similarity index 97%
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index f62c459..86893b5 100644
--- a/assets/papers_2024_hannon.md.Yb1uIpIV.lean.js
+++ b/assets/papers_2024_hannon.md.H8YxJdJi.lean.js
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-import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_hannon.html"}]]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function l(u,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",l]]);export{g as __pageData,v as default};
+import{_ as a,c as o,o as n,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","description":"","frontmatter":{"layout":"paper","title":"dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets","date":"2024-07-17","authors":["William W Hannon","Jesse D Bloom"],"journal":"Journal of Open Source Software","doi":"10.21105/joss.06129","link":"https://joss.theoj.org/papers/10.21105/joss.06129","image":"/assets/papers/2024_hannon.jpg","keywords":["Software tools","Deep mutational scanning"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_hannon.html"}]]},"headers":[],"relativePath":"papers/2024_hannon.md","filePath":"papers/2024_hannon.md"}'),s={name:"papers/2024_hannon.md"},i=e("h2",{id:"abstract",tabindex:"-1"},[t("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,"Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).",-1),d=e("p",null,[t("The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See "),e("a",{href:"https://dms-viz.github.io/",target:"_blank",rel:"noreferrer"},"https://dms-viz.github.io/"),t(" to use dms-viz.")],-1),c=[i,r,d];function l(u,h,p,m,f,b){return n(),o("div",null,c)}const v=a(s,[["render",l]]);export{g as __pageData,v as default};
diff --git a/assets/papers_2024_larsen.md.CU_Si900.js b/assets/papers_2024_larsen.md.BRHZbN3e.js
similarity index 94%
rename from assets/papers_2024_larsen.md.CU_Si900.js
rename to assets/papers_2024_larsen.md.BRHZbN3e.js
index 500972e..7cef876 100644
--- a/assets/papers_2024_larsen.md.CU_Si900.js
+++ b/assets/papers_2024_larsen.md.BRHZbN3e.js
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-import{_ as a,c as e,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_larsen.html"}]]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Nipah_Malaysia_RBP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Nipah_Malaysia_RBP_DMS/</a></p>',4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default};
+import{_ as a,c as e,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_larsen.html"}]]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i('<h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Nipah_Malaysia_RBP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Nipah_Malaysia_RBP_DMS/</a></p>',4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default};
diff --git a/assets/papers_2024_larsen.md.CU_Si900.lean.js b/assets/papers_2024_larsen.md.BRHZbN3e.lean.js
similarity index 88%
rename from assets/papers_2024_larsen.md.CU_Si900.lean.js
rename to assets/papers_2024_larsen.md.BRHZbN3e.lean.js
index 03c5462..94c1e6e 100644
--- a/assets/papers_2024_larsen.md.CU_Si900.lean.js
+++ b/assets/papers_2024_larsen.md.BRHZbN3e.lean.js
@@ -1 +1 @@
-import{_ as a,c as e,o as t,f as i}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_larsen.html"}]]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i("",4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default};
+import{_ as a,c as e,o as t,f as i}from"./chunks/framework.5XYse7Qj.js";const f=JSON.parse('{"title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","description":"","frontmatter":{"layout":"paper","title":"Functional and antigenic landscape of the Nipah virus receptor binding protein","date":"2024-04-17","authors":["Brendan B Larsen","Teagan McMahon","Jack T Brown","Zhaoqian Wang","Caelan E Radford","James E Crowe","David Veesler","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.04.17.589977","link":"https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract","image":"/assets/papers/2024_larsen.jpg","keywords":["Nipah","Deep mutational scanning","Pseudovirus"],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_larsen.html"}]]},"headers":[],"relativePath":"papers/2024_larsen.md","filePath":"papers/2024_larsen.md"}'),n={name:"papers/2024_larsen.md"},r=i("",4),o=[r];function s(l,c,p,d,h,u){return t(),e("div",null,o)}const m=a(n,[["render",s]]);export{f as __pageData,m as default};
diff --git a/assets/papers_2024_loes.md.Bza0-ndl.js b/assets/papers_2024_loes.md.Bza0-ndl.js
deleted file mode 100644
index d73a5ee..0000000
--- a/assets/papers_2024_loes.md.Bza0-ndl.js
+++ /dev/null
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-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_loes.html"}]]},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,h,c,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default};
diff --git a/assets/papers_2024_loes.md.Bza0-ndl.lean.js b/assets/papers_2024_loes.md.Bza0-ndl.lean.js
deleted file mode 100644
index d73a5ee..0000000
--- a/assets/papers_2024_loes.md.Bza0-ndl.lean.js
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-import{_ as t,c as i,o as n,b as e,d as a}from"./chunks/framework.B63u0Dcf.js";const f=JSON.parse('{"title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","description":"","frontmatter":{"layout":"paper","title":"High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains","date":"2024-03-08","authors":["Andrea N Loes","Rosario Araceli L Tarabi","John Huddleston","Lisa Touyon","Sook San Wong","Samuel MS Cheng","Nancy HL Leung","William W Hannon","Trevor Bedford","Sarah Cobey","Benjamin J Cowling","Jesse D Bloom"],"journal":"bioRxiv","doi":"10.1101/2024.03.08.584176","link":"https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract","image":"/assets/papers/2024_loes.jpg","keywords":["Influenza","Immunity"],"selected":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/papers/2024_loes.html"}]]},"headers":[],"relativePath":"papers/2024_loes.md","filePath":"papers/2024_loes.md"}'),s={name:"papers/2024_loes.md"},o=e("h2",{id:"abstract",tabindex:"-1"},[a("Abstract "),e("a",{class:"header-anchor",href:"#abstract","aria-label":'Permalink to "Abstract"'},"​")],-1),r=e("p",null,[a("The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: "),e("a",{href:"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1",target:"_blank",rel:"noreferrer"},"https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1"),a(") and a computational pipeline ("),e("a",{href:"https://github.com/jbloomlab/seqneut-pipeline",target:"_blank",rel:"noreferrer"},"https://github.com/jbloomlab/seqneut-pipeline"),a(") for the sequencing-based neutralization assays to facilitate the use of this method by others.")],-1),l=[o,r];function u(d,h,c,p,m,g){return n(),i("div",null,l)}const b=t(s,[["render",u]]);export{f as __pageData,b as default};
diff --git a/assets/papers_2024_loes.md.Dk1t25b0.js b/assets/papers_2024_loes.md.Dk1t25b0.js
new file mode 100644
index 0000000..cd3d7d5
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+import{_ as e,c as a,o as t,b as n}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Staff Scientist/Lab Manager","description":"","frontmatter":{"layout":"person","name":"Andrea Loes","image":"/assets/people/andrea-loes.jpg","title":"Staff Scientist/Lab Manager","category":"Staff","links":[{"link":"https://github.com/anloes","icon":"github"},{"link":"aloes@fredhutch.org","icon":"email"},{"link":"https://www.linkedin.com/in/andrea-loes-ph-d-59210419/","icon":"linkedin"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/andrea-loes.html"}]]},"headers":[],"relativePath":"people/andrea-loes.md","filePath":"people/andrea-loes.md"}'),o={name:"people/andrea-loes.md"},s=n("p",null,"Andrea Loes, PhD is a staff scientist/lab manager for the Bloom Lab. She recently developed a high-throughput, sequencing-based method for running neutralization assays for influenza viruses and is currently applying this method to better understand the sources of diversity in the specificity of human serum antibodies to influenza viruses between different individuals.",-1),i=[s];function r(l,d,c,p,h,f){return t(),a("div",null,i)}const g=e(o,[["render",r]]);export{m as __pageData,g as default};
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+import{_ as e,c as t,o,b as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"},{"link":"https://andrewwbutler.com","icon":"website"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/andrew-butler.html"}]]},"headers":[],"relativePath":"people/andrew-butler.md","filePath":"people/andrew-butler.md"}'),l={name:"people/andrew-butler.md"},r=n("p",null,"As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.",-1),a=[r];function s(i,c,d,p,u,h){return o(),t("div",null,a)}const _=e(l,[["render",s]]);export{b as __pageData,_ as default};
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+import{_ as e,c as t,o,b as n}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Andrew Butler","image":"/assets/people/andrew-butler.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/andrewwbutler","icon":"github"},{"link":"abutler@fredhutch.org","icon":"email"},{"link":"https://andrewwbutler.com","icon":"website"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/andrew-butler.html"}]]},"headers":[],"relativePath":"people/andrew-butler.md","filePath":"people/andrew-butler.md"}'),l={name:"people/andrew-butler.md"},r=n("p",null,"As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.",-1),a=[r];function s(i,c,d,p,u,h){return o(),t("div",null,a)}const _=e(l,[["render",s]]);export{b as __pageData,_ as default};
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similarity index 86%
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index 60674f6..8ad831e 100644
--- a/assets/people_arjun-aditham.md.BiOftMuQ.js
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+import{_ as a,c as t,o as e,b as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Arjun Aditham","image":"/assets/people/arjun-aditham.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/arjunaditham","icon":"github"},{"link":"aaditham@fredhutch.org","icon":"email"},{"link":"https://www.linkedin.com/in/arjun-aditham/","icon":"linkedin"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/arjun-aditham.html"}]]},"headers":[],"relativePath":"people/arjun-aditham.md","filePath":"people/arjun-aditham.md"}'),n={name:"people/arjun-aditham.md"},i=o("p",null,"As a postdoc in the Bloom Lab, I'm utilizing deep mutational scanning approaches to characterize the Rabies glycoprotein.",-1),l=[i];function r(s,c,d,p,h,m){return e(),t("div",null,l)}const g=a(n,[["render",r]]);export{_ as __pageData,g as default};
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+++ b/assets/people_bernadeta-dadonaite.md.BT3Wf7w6.js
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diff --git a/assets/people_brendan-larsen.md.sJhvjY3G.js b/assets/people_brendan-larsen.md.DWaAm88D.js
similarity index 89%
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--- a/assets/people_brendan-larsen.md.sJhvjY3G.js
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@@ -1 +1 @@
-import{_ as e,c as n,o as t,b as o}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Brendan Larsen","image":"/assets/people/brendan-larsen.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/bblarsen-sci","icon":"github"},{"link":"https://x.com/bblarsen1","icon":"twitter"},{"link":"https://bblarsen-sci.github.io/about/","icon":"website"},{"link":"blarsen@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/brendan-larsen.html"}]]},"headers":[],"relativePath":"people/brendan-larsen.md","filePath":"people/brendan-larsen.md"}'),a={name:"people/brendan-larsen.md"},s=o("p",null,"Brendan Larsen is a Postdoctoral Fellow in the Bloom lab, where he studies the functional and antigenic evolution of Nipah virus. He is broadly interested in zoonotic viruses, in particular, bat and rodent-borne viruses that could potentially spillover into humans. He is funded by the Washington Research Foundation.",-1),r=[s];function l(i,c,d,p,h,b){return t(),n("div",null,r)}const _=e(a,[["render",l]]);export{m as __pageData,_ as default};
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similarity index 89%
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+import{_ as e,c as n,o as t,b as o}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Brendan Larsen","image":"/assets/people/brendan-larsen.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/bblarsen-sci","icon":"github"},{"link":"https://x.com/bblarsen1","icon":"twitter"},{"link":"https://bblarsen-sci.github.io/about/","icon":"website"},{"link":"blarsen@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/brendan-larsen.html"}]]},"headers":[],"relativePath":"people/brendan-larsen.md","filePath":"people/brendan-larsen.md"}'),a={name:"people/brendan-larsen.md"},s=o("p",null,"Brendan Larsen is a Postdoctoral Fellow in the Bloom lab, where he studies the functional and antigenic evolution of Nipah virus. He is broadly interested in zoonotic viruses, in particular, bat and rodent-borne viruses that could potentially spillover into humans. He is funded by the Washington Research Foundation.",-1),r=[s];function l(i,c,d,p,h,b){return t(),n("div",null,r)}const _=e(a,[["render",l]]);export{m as __pageData,_ as default};
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+import{_ as a,c as e,o as t}from"./chunks/framework.5XYse7Qj.js";const s=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caelan-radford.html"}]]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),o={name:"people/caelan-radford.md"};function n(r,l,c,d,i,f){return t(),e("div")}const m=a(o,[["render",n]]);export{s as __pageData,m as default};
diff --git a/assets/people_caelan-radford.md.C1vHBlIv.lean.js b/assets/people_caelan-radford.md.L3tL8HC2.lean.js
similarity index 92%
rename from assets/people_caelan-radford.md.C1vHBlIv.lean.js
rename to assets/people_caelan-radford.md.L3tL8HC2.lean.js
index f380e97..1dcebc4 100644
--- a/assets/people_caelan-radford.md.C1vHBlIv.lean.js
+++ b/assets/people_caelan-radford.md.L3tL8HC2.lean.js
@@ -1 +1 @@
-import{_ as a,c as e,o as t}from"./chunks/framework.B63u0Dcf.js";const s=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caelan-radford.html"}]]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),o={name:"people/caelan-radford.md"};function n(r,l,c,d,i,f){return t(),e("div")}const m=a(o,[["render",n]]);export{s as __pageData,m as default};
+import{_ as a,c as e,o as t}from"./chunks/framework.5XYse7Qj.js";const s=JSON.parse('{"title":"Staff Scientist","description":"","frontmatter":{"layout":"person","name":"Caelan Radford","image":"/assets/people/caelan-radford.jpg","title":"Staff Scientist","category":"Staff","links":[{"link":"https://github.com/caelanradford","icon":"github"},{"link":"https://www.linkedin.com/in/caelan-radford-a51b61b3/","icon":"linkedin"},{"link":"ceradfor@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caelan-radford.html"}]]},"headers":[],"relativePath":"people/caelan-radford.md","filePath":"people/caelan-radford.md"}'),o={name:"people/caelan-radford.md"};function n(r,l,c,d,i,f){return t(),e("div")}const m=a(o,[["render",n]]);export{s as __pageData,m as default};
diff --git a/assets/people_caleb-carr.md.aC_xwRdH.js b/assets/people_caleb-carr.md.UxCJaYDB.js
similarity index 85%
rename from assets/people_caleb-carr.md.aC_xwRdH.js
rename to assets/people_caleb-carr.md.UxCJaYDB.js
index 26af56f..ea2d510 100644
--- a/assets/people_caleb-carr.md.aC_xwRdH.js
+++ b/assets/people_caleb-carr.md.UxCJaYDB.js
@@ -1 +1 @@
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+import{_ as e,c as a,o as t,b as r}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caleb Carr","image":"/assets/people/caleb-carr.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/Caleb-Carr","icon":"github"},{"link":"ccarr@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caleb-carr.html"}]]},"headers":[],"relativePath":"people/caleb-carr.md","filePath":"people/caleb-carr.md"}'),o={name:"people/caleb-carr.md"},l=r("p",null,"As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.",-1),c=[l];function n(s,i,p,d,u,m){return t(),a("div",null,c)}const b=e(o,[["render",n]]);export{_ as __pageData,b as default};
diff --git a/assets/people_caleb-carr.md.aC_xwRdH.lean.js b/assets/people_caleb-carr.md.UxCJaYDB.lean.js
similarity index 85%
rename from assets/people_caleb-carr.md.aC_xwRdH.lean.js
rename to assets/people_caleb-carr.md.UxCJaYDB.lean.js
index 26af56f..ea2d510 100644
--- a/assets/people_caleb-carr.md.aC_xwRdH.lean.js
+++ b/assets/people_caleb-carr.md.UxCJaYDB.lean.js
@@ -1 +1 @@
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+import{_ as e,c as a,o as t,b as r}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caleb Carr","image":"/assets/people/caleb-carr.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/Caleb-Carr","icon":"github"},{"link":"ccarr@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caleb-carr.html"}]]},"headers":[],"relativePath":"people/caleb-carr.md","filePath":"people/caleb-carr.md"}'),o={name:"people/caleb-carr.md"},l=r("p",null,"As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.",-1),c=[l];function n(s,i,p,d,u,m){return t(),a("div",null,c)}const b=e(o,[["render",n]]);export{_ as __pageData,b as default};
diff --git a/assets/people_caroline-kikawa.md.CeAz53FR.js b/assets/people_caroline-kikawa.md.DIdlpr35.js
similarity index 88%
rename from assets/people_caroline-kikawa.md.CeAz53FR.js
rename to assets/people_caroline-kikawa.md.DIdlpr35.js
index f16a3f8..7d068b3 100644
--- a/assets/people_caroline-kikawa.md.CeAz53FR.js
+++ b/assets/people_caroline-kikawa.md.DIdlpr35.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t,b as n}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caroline-kikawa.html"}]]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),o={name:"people/caroline-kikawa.md"},i=n("p",null,"I'm a graduate student in the Bloom lab using high-throughput sequencing-based neutralization assays to profile human neutralizing antibody responses to seasonal influenza viruses. More broadly, I'm interested in understanding factors that impact influenza virus antigenic evolution and methods to improve forecasting.",-1),r=[i];function s(l,c,d,p,u,h){return t(),a("div",null,r)}const g=e(o,[["render",s]]);export{m as __pageData,g as default};
+import{_ as e,c as a,o as t,b as n}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caroline-kikawa.html"}]]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),o={name:"people/caroline-kikawa.md"},i=n("p",null,"I'm a graduate student in the Bloom lab using high-throughput sequencing-based neutralization assays to profile human neutralizing antibody responses to seasonal influenza viruses. More broadly, I'm interested in understanding factors that impact influenza virus antigenic evolution and methods to improve forecasting.",-1),r=[i];function s(l,c,d,p,u,h){return t(),a("div",null,r)}const g=e(o,[["render",s]]);export{m as __pageData,g as default};
diff --git a/assets/people_caroline-kikawa.md.CeAz53FR.lean.js b/assets/people_caroline-kikawa.md.DIdlpr35.lean.js
similarity index 88%
rename from assets/people_caroline-kikawa.md.CeAz53FR.lean.js
rename to assets/people_caroline-kikawa.md.DIdlpr35.lean.js
index f16a3f8..7d068b3 100644
--- a/assets/people_caroline-kikawa.md.CeAz53FR.lean.js
+++ b/assets/people_caroline-kikawa.md.DIdlpr35.lean.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t,b as n}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caroline-kikawa.html"}]]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),o={name:"people/caroline-kikawa.md"},i=n("p",null,"I'm a graduate student in the Bloom lab using high-throughput sequencing-based neutralization assays to profile human neutralizing antibody responses to seasonal influenza viruses. More broadly, I'm interested in understanding factors that impact influenza virus antigenic evolution and methods to improve forecasting.",-1),r=[i];function s(l,c,d,p,u,h){return t(),a("div",null,r)}const g=e(o,[["render",s]]);export{m as __pageData,g as default};
+import{_ as e,c as a,o as t,b as n}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Caroline Kikawa","image":"/assets/people/caroline-kikawa.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/ckikawa","icon":"github"},{"link":"ckikawa@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/caroline-kikawa.html"}]]},"headers":[],"relativePath":"people/caroline-kikawa.md","filePath":"people/caroline-kikawa.md"}'),o={name:"people/caroline-kikawa.md"},i=n("p",null,"I'm a graduate student in the Bloom lab using high-throughput sequencing-based neutralization assays to profile human neutralizing antibody responses to seasonal influenza viruses. More broadly, I'm interested in understanding factors that impact influenza virus antigenic evolution and methods to improve forecasting.",-1),r=[i];function s(l,c,d,p,u,h){return t(),a("div",null,r)}const g=e(o,[["render",s]]);export{m as __pageData,g as default};
diff --git a/assets/people_cassandra-simonich.md.N3uaFzQT.js b/assets/people_cassandra-simonich.md.C4HLF-go.js
similarity index 87%
rename from assets/people_cassandra-simonich.md.N3uaFzQT.js
rename to assets/people_cassandra-simonich.md.C4HLF-go.js
index c94b7c5..c1668bc 100644
--- a/assets/people_cassandra-simonich.md.N3uaFzQT.js
+++ b/assets/people_cassandra-simonich.md.C4HLF-go.js
@@ -1 +1 @@
-import{_ as e,c as s,o as a,b as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Pediatric Infectious Disease Fellow","description":"","frontmatter":{"layout":"person","name":"Cassandra Simonich","image":"/assets/people/cassandra-simonich.jpg","title":"Pediatric Infectious Disease Fellow","category":"Postdocs","links":[{"link":"https://github.com/CSimonich","icon":"github"},{"link":"Cassandra.simonich@seattlechildrens.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/cassandra-simonich.html"}]]},"headers":[],"relativePath":"people/cassandra-simonich.md","filePath":"people/cassandra-simonich.md"}'),o={name:"people/cassandra-simonich.md"},t=i("p",null,"Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.",-1),n=[t];function c(l,r,d,h,p,m){return a(),s("div",null,n)}const f=e(o,[["render",c]]);export{_ as __pageData,f as default};
+import{_ as e,c as s,o as a,b as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Pediatric Infectious Disease Fellow","description":"","frontmatter":{"layout":"person","name":"Cassandra Simonich","image":"/assets/people/cassandra-simonich.jpg","title":"Pediatric Infectious Disease Fellow","category":"Postdocs","links":[{"link":"https://github.com/CSimonich","icon":"github"},{"link":"Cassandra.simonich@seattlechildrens.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/cassandra-simonich.html"}]]},"headers":[],"relativePath":"people/cassandra-simonich.md","filePath":"people/cassandra-simonich.md"}'),o={name:"people/cassandra-simonich.md"},t=i("p",null,"Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.",-1),n=[t];function c(l,r,d,h,p,m){return a(),s("div",null,n)}const f=e(o,[["render",c]]);export{_ as __pageData,f as default};
diff --git a/assets/people_cassandra-simonich.md.N3uaFzQT.lean.js b/assets/people_cassandra-simonich.md.C4HLF-go.lean.js
similarity index 87%
rename from assets/people_cassandra-simonich.md.N3uaFzQT.lean.js
rename to assets/people_cassandra-simonich.md.C4HLF-go.lean.js
index c94b7c5..c1668bc 100644
--- a/assets/people_cassandra-simonich.md.N3uaFzQT.lean.js
+++ b/assets/people_cassandra-simonich.md.C4HLF-go.lean.js
@@ -1 +1 @@
-import{_ as e,c as s,o as a,b as i}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Pediatric Infectious Disease Fellow","description":"","frontmatter":{"layout":"person","name":"Cassandra Simonich","image":"/assets/people/cassandra-simonich.jpg","title":"Pediatric Infectious Disease Fellow","category":"Postdocs","links":[{"link":"https://github.com/CSimonich","icon":"github"},{"link":"Cassandra.simonich@seattlechildrens.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/cassandra-simonich.html"}]]},"headers":[],"relativePath":"people/cassandra-simonich.md","filePath":"people/cassandra-simonich.md"}'),o={name:"people/cassandra-simonich.md"},t=i("p",null,"Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.",-1),n=[t];function c(l,r,d,h,p,m){return a(),s("div",null,n)}const f=e(o,[["render",c]]);export{_ as __pageData,f as default};
+import{_ as e,c as s,o as a,b as i}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Pediatric Infectious Disease Fellow","description":"","frontmatter":{"layout":"person","name":"Cassandra Simonich","image":"/assets/people/cassandra-simonich.jpg","title":"Pediatric Infectious Disease Fellow","category":"Postdocs","links":[{"link":"https://github.com/CSimonich","icon":"github"},{"link":"Cassandra.simonich@seattlechildrens.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/cassandra-simonich.html"}]]},"headers":[],"relativePath":"people/cassandra-simonich.md","filePath":"people/cassandra-simonich.md"}'),o={name:"people/cassandra-simonich.md"},t=i("p",null,"Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.",-1),n=[t];function c(l,r,d,h,p,m){return a(),s("div",null,n)}const f=e(o,[["render",c]]);export{_ as __pageData,f as default};
diff --git a/assets/people_catherine-jacob-dolan.md.BQRa4VNL.js b/assets/people_catherine-jacob-dolan.md.fes_GaPS.js
similarity index 85%
rename from assets/people_catherine-jacob-dolan.md.BQRa4VNL.js
rename to assets/people_catherine-jacob-dolan.md.fes_GaPS.js
index 841f2a2..f65020f 100644
--- a/assets/people_catherine-jacob-dolan.md.BQRa4VNL.js
+++ b/assets/people_catherine-jacob-dolan.md.fes_GaPS.js
@@ -1 +1 @@
-import{_ as e,c as o,o as a,b as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Catherine Jacob-Dolan","image":"/assets/people/catherine-jacob-dolan.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/CJ-D","icon":"github"},{"link":"cjacobdo@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/catherine-jacob-dolan.html"}]]},"headers":[],"relativePath":"people/catherine-jacob-dolan.md","filePath":"people/catherine-jacob-dolan.md"}'),l={name:"people/catherine-jacob-dolan.md"},n=t("p",null,"Catherine is a new Postdoctoral Fellow in the Bloom lab.",-1),c=[n];function r(s,i,p,d,h,m){return a(),o("div",null,c)}const f=e(l,[["render",r]]);export{b as __pageData,f as default};
+import{_ as e,c as o,o as a,b as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Catherine Jacob-Dolan","image":"/assets/people/catherine-jacob-dolan.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/CJ-D","icon":"github"},{"link":"cjacobdo@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/catherine-jacob-dolan.html"}]]},"headers":[],"relativePath":"people/catherine-jacob-dolan.md","filePath":"people/catherine-jacob-dolan.md"}'),l={name:"people/catherine-jacob-dolan.md"},n=t("p",null,"Catherine is a new Postdoctoral Fellow in the Bloom lab.",-1),c=[n];function r(s,i,p,d,h,m){return a(),o("div",null,c)}const f=e(l,[["render",r]]);export{b as __pageData,f as default};
diff --git a/assets/people_catherine-jacob-dolan.md.BQRa4VNL.lean.js b/assets/people_catherine-jacob-dolan.md.fes_GaPS.lean.js
similarity index 85%
rename from assets/people_catherine-jacob-dolan.md.BQRa4VNL.lean.js
rename to assets/people_catherine-jacob-dolan.md.fes_GaPS.lean.js
index 841f2a2..f65020f 100644
--- a/assets/people_catherine-jacob-dolan.md.BQRa4VNL.lean.js
+++ b/assets/people_catherine-jacob-dolan.md.fes_GaPS.lean.js
@@ -1 +1 @@
-import{_ as e,c as o,o as a,b as t}from"./chunks/framework.B63u0Dcf.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Catherine Jacob-Dolan","image":"/assets/people/catherine-jacob-dolan.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/CJ-D","icon":"github"},{"link":"cjacobdo@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/catherine-jacob-dolan.html"}]]},"headers":[],"relativePath":"people/catherine-jacob-dolan.md","filePath":"people/catherine-jacob-dolan.md"}'),l={name:"people/catherine-jacob-dolan.md"},n=t("p",null,"Catherine is a new Postdoctoral Fellow in the Bloom lab.",-1),c=[n];function r(s,i,p,d,h,m){return a(),o("div",null,c)}const f=e(l,[["render",r]]);export{b as __pageData,f as default};
+import{_ as e,c as o,o as a,b as t}from"./chunks/framework.5XYse7Qj.js";const b=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Catherine Jacob-Dolan","image":"/assets/people/catherine-jacob-dolan.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/CJ-D","icon":"github"},{"link":"cjacobdo@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/catherine-jacob-dolan.html"}]]},"headers":[],"relativePath":"people/catherine-jacob-dolan.md","filePath":"people/catherine-jacob-dolan.md"}'),l={name:"people/catherine-jacob-dolan.md"},n=t("p",null,"Catherine is a new Postdoctoral Fellow in the Bloom lab.",-1),c=[n];function r(s,i,p,d,h,m){return a(),o("div",null,c)}const f=e(l,[["render",r]]);export{b as __pageData,f as default};
diff --git a/assets/people_index.md.dxcleK8f.js b/assets/people_index.md.ScZkUJ_c.js
similarity index 85%
rename from assets/people_index.md.dxcleK8f.js
rename to assets/people_index.md.ScZkUJ_c.js
index cfff6b0..4eba14d 100644
--- a/assets/people_index.md.dxcleK8f.js
+++ b/assets/people_index.md.ScZkUJ_c.js
@@ -1 +1 @@
-import{_ as e,c as t,o as a}from"./chunks/framework.B63u0Dcf.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"team":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/"}]]},"headers":[],"relativePath":"people/index.md","filePath":"people/index.md"}'),o={name:"people/index.md"};function n(r,p,c,s,i,l){return a(),t("div")}const _=e(o,[["render",n]]);export{m as __pageData,_ as default};
+import{_ as e,c as t,o as a}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"team":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/"}]]},"headers":[],"relativePath":"people/index.md","filePath":"people/index.md"}'),o={name:"people/index.md"};function n(r,p,c,s,i,l){return a(),t("div")}const _=e(o,[["render",n]]);export{m as __pageData,_ as default};
diff --git a/assets/people_index.md.dxcleK8f.lean.js b/assets/people_index.md.ScZkUJ_c.lean.js
similarity index 85%
rename from assets/people_index.md.dxcleK8f.lean.js
rename to assets/people_index.md.ScZkUJ_c.lean.js
index cfff6b0..4eba14d 100644
--- a/assets/people_index.md.dxcleK8f.lean.js
+++ b/assets/people_index.md.ScZkUJ_c.lean.js
@@ -1 +1 @@
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+import{_ as e,c as t,o as a}from"./chunks/framework.5XYse7Qj.js";const m=JSON.parse('{"title":"","description":"","frontmatter":{"team":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/"}]]},"headers":[],"relativePath":"people/index.md","filePath":"people/index.md"}'),o={name:"people/index.md"};function n(r,p,c,s,i,l){return a(),t("div")}const _=e(o,[["render",n]]);export{m as __pageData,_ as default};
diff --git a/assets/people_jenny-ahn.md.DVfUZVEG.lean.js b/assets/people_jenny-ahn.md.BfO8hFLZ.js
similarity index 88%
rename from assets/people_jenny-ahn.md.DVfUZVEG.lean.js
rename to assets/people_jenny-ahn.md.BfO8hFLZ.js
index 444b045..69a2dda 100644
--- a/assets/people_jenny-ahn.md.DVfUZVEG.lean.js
+++ b/assets/people_jenny-ahn.md.BfO8hFLZ.js
@@ -1 +1 @@
-import{_ as e,c as n,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Jenny Ahn","image":"/assets/people/jenny-ahn.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/jennyahn0","icon":"github"},{"link":"https://www.linkedin.com/in/jennyahn0/","icon":"linkedin"},{"link":"jennyahn@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jenny-ahn.html"}]]},"headers":[],"relativePath":"people/jenny-ahn.md","filePath":"people/jenny-ahn.md"}'),o={name:"people/jenny-ahn.md"},i=a("p",null,"As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.",-1),l=[i];function s(r,p,d,c,h,u){return t(),n("div",null,l)}const y=e(o,[["render",s]]);export{_ as __pageData,y as default};
+import{_ as e,c as n,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Jenny Ahn","image":"/assets/people/jenny-ahn.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/jennyahn0","icon":"github"},{"link":"https://www.linkedin.com/in/jennyahn0/","icon":"linkedin"},{"link":"jennyahn@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jenny-ahn.html"}]]},"headers":[],"relativePath":"people/jenny-ahn.md","filePath":"people/jenny-ahn.md"}'),o={name:"people/jenny-ahn.md"},i=a("p",null,"As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.",-1),l=[i];function s(r,p,d,c,h,u){return t(),n("div",null,l)}const y=e(o,[["render",s]]);export{_ as __pageData,y as default};
diff --git a/assets/people_jenny-ahn.md.DVfUZVEG.js b/assets/people_jenny-ahn.md.BfO8hFLZ.lean.js
similarity index 88%
rename from assets/people_jenny-ahn.md.DVfUZVEG.js
rename to assets/people_jenny-ahn.md.BfO8hFLZ.lean.js
index 444b045..69a2dda 100644
--- a/assets/people_jenny-ahn.md.DVfUZVEG.js
+++ b/assets/people_jenny-ahn.md.BfO8hFLZ.lean.js
@@ -1 +1 @@
-import{_ as e,c as n,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Jenny Ahn","image":"/assets/people/jenny-ahn.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/jennyahn0","icon":"github"},{"link":"https://www.linkedin.com/in/jennyahn0/","icon":"linkedin"},{"link":"jennyahn@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jenny-ahn.html"}]]},"headers":[],"relativePath":"people/jenny-ahn.md","filePath":"people/jenny-ahn.md"}'),o={name:"people/jenny-ahn.md"},i=a("p",null,"As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.",-1),l=[i];function s(r,p,d,c,h,u){return t(),n("div",null,l)}const y=e(o,[["render",s]]);export{_ as __pageData,y as default};
+import{_ as e,c as n,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Jenny Ahn","image":"/assets/people/jenny-ahn.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/jennyahn0","icon":"github"},{"link":"https://www.linkedin.com/in/jennyahn0/","icon":"linkedin"},{"link":"jennyahn@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jenny-ahn.html"}]]},"headers":[],"relativePath":"people/jenny-ahn.md","filePath":"people/jenny-ahn.md"}'),o={name:"people/jenny-ahn.md"},i=a("p",null,"As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.",-1),l=[i];function s(r,p,d,c,h,u){return t(),n("div",null,l)}const y=e(o,[["render",s]]);export{_ as __pageData,y as default};
diff --git a/assets/people_jesse-bloom.md.BhfmpoeK.js b/assets/people_jesse-bloom.md.BF5LKx3g.js
similarity index 91%
rename from assets/people_jesse-bloom.md.BhfmpoeK.js
rename to assets/people_jesse-bloom.md.BF5LKx3g.js
index 6213f66..7a57574 100644
--- a/assets/people_jesse-bloom.md.BhfmpoeK.js
+++ b/assets/people_jesse-bloom.md.BF5LKx3g.js
@@ -1 +1 @@
-import{_ as e,c as o,o as t,b as i}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Principal Investigator","description":"","frontmatter":{"layout":"person","name":"Jesse Bloom","image":"/assets/people/jesse-bloom.jpg","title":"Principal Investigator","category":"Faculty","links":[{"link":"https://github.com/jbloom","icon":"github"},{"link":"https://twitter.com/jbloom_lab?lang=en","icon":"twitter"},{"link":"jbloom@fredhutch.org","icon":"email"},{"link":"https://scholar.google.com/citations?user=S12x_eQAAAAJ","icon":"scholar"},{"link":"https://orcid.org/0000-0003-1267-3408","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jesse-bloom.html"}]]},"headers":[],"relativePath":"people/jesse-bloom.md","filePath":"people/jesse-bloom.md"}'),s={name:"people/jesse-bloom.md"},a=i("p",null,"Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).",-1),r=[a];function n(l,h,c,d,m,p){return t(),o("div",null,r)}const _=e(s,[["render",n]]);export{u as __pageData,_ as default};
+import{_ as e,c as o,o as t,b as i}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Principal Investigator","description":"","frontmatter":{"layout":"person","name":"Jesse Bloom","image":"/assets/people/jesse-bloom.jpg","title":"Principal Investigator","category":"Faculty","links":[{"link":"https://github.com/jbloom","icon":"github"},{"link":"https://twitter.com/jbloom_lab?lang=en","icon":"twitter"},{"link":"jbloom@fredhutch.org","icon":"email"},{"link":"https://scholar.google.com/citations?user=S12x_eQAAAAJ","icon":"scholar"},{"link":"https://orcid.org/0000-0003-1267-3408","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jesse-bloom.html"}]]},"headers":[],"relativePath":"people/jesse-bloom.md","filePath":"people/jesse-bloom.md"}'),s={name:"people/jesse-bloom.md"},a=i("p",null,"Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).",-1),r=[a];function n(l,h,c,d,m,p){return t(),o("div",null,r)}const _=e(s,[["render",n]]);export{u as __pageData,_ as default};
diff --git a/assets/people_jesse-bloom.md.BhfmpoeK.lean.js b/assets/people_jesse-bloom.md.BF5LKx3g.lean.js
similarity index 91%
rename from assets/people_jesse-bloom.md.BhfmpoeK.lean.js
rename to assets/people_jesse-bloom.md.BF5LKx3g.lean.js
index 6213f66..7a57574 100644
--- a/assets/people_jesse-bloom.md.BhfmpoeK.lean.js
+++ b/assets/people_jesse-bloom.md.BF5LKx3g.lean.js
@@ -1 +1 @@
-import{_ as e,c as o,o as t,b as i}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Principal Investigator","description":"","frontmatter":{"layout":"person","name":"Jesse Bloom","image":"/assets/people/jesse-bloom.jpg","title":"Principal Investigator","category":"Faculty","links":[{"link":"https://github.com/jbloom","icon":"github"},{"link":"https://twitter.com/jbloom_lab?lang=en","icon":"twitter"},{"link":"jbloom@fredhutch.org","icon":"email"},{"link":"https://scholar.google.com/citations?user=S12x_eQAAAAJ","icon":"scholar"},{"link":"https://orcid.org/0000-0003-1267-3408","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jesse-bloom.html"}]]},"headers":[],"relativePath":"people/jesse-bloom.md","filePath":"people/jesse-bloom.md"}'),s={name:"people/jesse-bloom.md"},a=i("p",null,"Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).",-1),r=[a];function n(l,h,c,d,m,p){return t(),o("div",null,r)}const _=e(s,[["render",n]]);export{u as __pageData,_ as default};
+import{_ as e,c as o,o as t,b as i}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Principal Investigator","description":"","frontmatter":{"layout":"person","name":"Jesse Bloom","image":"/assets/people/jesse-bloom.jpg","title":"Principal Investigator","category":"Faculty","links":[{"link":"https://github.com/jbloom","icon":"github"},{"link":"https://twitter.com/jbloom_lab?lang=en","icon":"twitter"},{"link":"jbloom@fredhutch.org","icon":"email"},{"link":"https://scholar.google.com/citations?user=S12x_eQAAAAJ","icon":"scholar"},{"link":"https://orcid.org/0000-0003-1267-3408","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/jesse-bloom.html"}]]},"headers":[],"relativePath":"people/jesse-bloom.md","filePath":"people/jesse-bloom.md"}'),s={name:"people/jesse-bloom.md"},a=i("p",null,"Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).",-1),r=[a];function n(l,h,c,d,m,p){return t(),o("div",null,r)}const _=e(s,[["render",n]]);export{u as __pageData,_ as default};
diff --git a/assets/people_lizzie-plender.md.B6O1hUSG.js b/assets/people_lizzie-plender.md.Drv_xT1b.js
similarity index 94%
rename from assets/people_lizzie-plender.md.B6O1hUSG.js
rename to assets/people_lizzie-plender.md.Drv_xT1b.js
index 0050161..f15ccc5 100644
--- a/assets/people_lizzie-plender.md.B6O1hUSG.js
+++ b/assets/people_lizzie-plender.md.Drv_xT1b.js
@@ -1 +1 @@
-import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lizzie Plender","image":"/assets/people/lizzie-plender.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/plendere","icon":"github"},{"link":"plendere@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lizzie-plender.html"}]]},"headers":[],"relativePath":"people/lizzie-plender.md","filePath":"people/lizzie-plender.md"}'),l={name:"people/lizzie-plender.md"},r=e("p",null,[t("Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease."),e("br"),t(" Lizzie is joint-advised by "),e("a",{href:"https://eichlerlab.gs.washington.edu/index.html",target:"_blank",rel:"noreferrer"},"Evan Eichler"),t(".")],-1),o=[r];function s(d,p,c,h,u,m){return a(),n("div",null,o)}const g=i(l,[["render",s]]);export{_ as __pageData,g as default};
+import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lizzie Plender","image":"/assets/people/lizzie-plender.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/plendere","icon":"github"},{"link":"plendere@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lizzie-plender.html"}]]},"headers":[],"relativePath":"people/lizzie-plender.md","filePath":"people/lizzie-plender.md"}'),l={name:"people/lizzie-plender.md"},r=e("p",null,[t("Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease."),e("br"),t(" Lizzie is joint-advised by "),e("a",{href:"https://eichlerlab.gs.washington.edu/index.html",target:"_blank",rel:"noreferrer"},"Evan Eichler"),t(".")],-1),o=[r];function s(d,p,c,h,u,m){return a(),n("div",null,o)}const g=i(l,[["render",s]]);export{_ as __pageData,g as default};
diff --git a/assets/people_lizzie-plender.md.B6O1hUSG.lean.js b/assets/people_lizzie-plender.md.Drv_xT1b.lean.js
similarity index 94%
rename from assets/people_lizzie-plender.md.B6O1hUSG.lean.js
rename to assets/people_lizzie-plender.md.Drv_xT1b.lean.js
index 0050161..f15ccc5 100644
--- a/assets/people_lizzie-plender.md.B6O1hUSG.lean.js
+++ b/assets/people_lizzie-plender.md.Drv_xT1b.lean.js
@@ -1 +1 @@
-import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lizzie Plender","image":"/assets/people/lizzie-plender.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/plendere","icon":"github"},{"link":"plendere@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lizzie-plender.html"}]]},"headers":[],"relativePath":"people/lizzie-plender.md","filePath":"people/lizzie-plender.md"}'),l={name:"people/lizzie-plender.md"},r=e("p",null,[t("Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease."),e("br"),t(" Lizzie is joint-advised by "),e("a",{href:"https://eichlerlab.gs.washington.edu/index.html",target:"_blank",rel:"noreferrer"},"Evan Eichler"),t(".")],-1),o=[r];function s(d,p,c,h,u,m){return a(),n("div",null,o)}const g=i(l,[["render",s]]);export{_ as __pageData,g as default};
+import{_ as i,c as n,o as a,b as e,d as t}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lizzie Plender","image":"/assets/people/lizzie-plender.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/plendere","icon":"github"},{"link":"plendere@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lizzie-plender.html"}]]},"headers":[],"relativePath":"people/lizzie-plender.md","filePath":"people/lizzie-plender.md"}'),l={name:"people/lizzie-plender.md"},r=e("p",null,[t("Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease."),e("br"),t(" Lizzie is joint-advised by "),e("a",{href:"https://eichlerlab.gs.washington.edu/index.html",target:"_blank",rel:"noreferrer"},"Evan Eichler"),t(".")],-1),o=[r];function s(d,p,c,h,u,m){return a(),n("div",null,o)}const g=i(l,[["render",s]]);export{_ as __pageData,g as default};
diff --git a/assets/people_lucas-kampman.md.smFgburF.js b/assets/people_lucas-kampman.md.DenqELKd.js
similarity index 91%
rename from assets/people_lucas-kampman.md.smFgburF.js
rename to assets/people_lucas-kampman.md.DenqELKd.js
index 224e561..fc03005 100644
--- a/assets/people_lucas-kampman.md.smFgburF.js
+++ b/assets/people_lucas-kampman.md.DenqELKd.js
@@ -1 +1 @@
-import{_ as a,c as e,o as t}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lucas Kampman","image":"/assets/people/lucas-kampman.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/lucaskampman","icon":"github"},{"link":"kampman@uw.edu","icon":"email"},{"link":"https://orcid.org/0000-0002-2008-549X","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lucas-kampman.html"}]]},"headers":[],"relativePath":"people/lucas-kampman.md","filePath":"people/lucas-kampman.md"}'),n={name:"people/lucas-kampman.md"};function o(p,m,s,c,l,r){return t(),e("div")}const d=a(n,[["render",o]]);export{u as __pageData,d as default};
+import{_ as a,c as e,o as t}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lucas Kampman","image":"/assets/people/lucas-kampman.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/lucaskampman","icon":"github"},{"link":"kampman@uw.edu","icon":"email"},{"link":"https://orcid.org/0000-0002-2008-549X","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lucas-kampman.html"}]]},"headers":[],"relativePath":"people/lucas-kampman.md","filePath":"people/lucas-kampman.md"}'),n={name:"people/lucas-kampman.md"};function o(p,m,s,c,l,r){return t(),e("div")}const d=a(n,[["render",o]]);export{u as __pageData,d as default};
diff --git a/assets/people_lucas-kampman.md.smFgburF.lean.js b/assets/people_lucas-kampman.md.DenqELKd.lean.js
similarity index 91%
rename from assets/people_lucas-kampman.md.smFgburF.lean.js
rename to assets/people_lucas-kampman.md.DenqELKd.lean.js
index 224e561..fc03005 100644
--- a/assets/people_lucas-kampman.md.smFgburF.lean.js
+++ b/assets/people_lucas-kampman.md.DenqELKd.lean.js
@@ -1 +1 @@
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+import{_ as a,c as e,o as t}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Lucas Kampman","image":"/assets/people/lucas-kampman.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/lucaskampman","icon":"github"},{"link":"kampman@uw.edu","icon":"email"},{"link":"https://orcid.org/0000-0002-2008-549X","icon":"orcid"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/lucas-kampman.html"}]]},"headers":[],"relativePath":"people/lucas-kampman.md","filePath":"people/lucas-kampman.md"}'),n={name:"people/lucas-kampman.md"};function o(p,m,s,c,l,r){return t(),e("div")}const d=a(n,[["render",o]]);export{u as __pageData,d as default};
diff --git a/assets/people_sara-sunshine.md.ZW6v3r7F.js b/assets/people_sara-sunshine.md.Mi-pXUXK.js
similarity index 91%
rename from assets/people_sara-sunshine.md.ZW6v3r7F.js
rename to assets/people_sara-sunshine.md.Mi-pXUXK.js
index 188fc73..d3a85d2 100644
--- a/assets/people_sara-sunshine.md.ZW6v3r7F.js
+++ b/assets/people_sara-sunshine.md.Mi-pXUXK.js
@@ -1 +1 @@
-import{_ as e,c as s,o as a}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sara Sunshine","image":"/assets/people/sara-sunshine.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com//Sara-Sunshine","icon":"github"},{"link":"ssunshin@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sara-sunshine.html"}]]},"headers":[],"relativePath":"people/sara-sunshine.md","filePath":"people/sara-sunshine.md"}'),n={name:"people/sara-sunshine.md"};function o(t,r,i,l,c,p){return a(),s("div")}const d=e(n,[["render",o]]);export{u as __pageData,d as default};
+import{_ as e,c as s,o as a}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sara Sunshine","image":"/assets/people/sara-sunshine.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com//Sara-Sunshine","icon":"github"},{"link":"ssunshin@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sara-sunshine.html"}]]},"headers":[],"relativePath":"people/sara-sunshine.md","filePath":"people/sara-sunshine.md"}'),n={name:"people/sara-sunshine.md"};function o(t,r,i,l,c,p){return a(),s("div")}const d=e(n,[["render",o]]);export{u as __pageData,d as default};
diff --git a/assets/people_sara-sunshine.md.ZW6v3r7F.lean.js b/assets/people_sara-sunshine.md.Mi-pXUXK.lean.js
similarity index 91%
rename from assets/people_sara-sunshine.md.ZW6v3r7F.lean.js
rename to assets/people_sara-sunshine.md.Mi-pXUXK.lean.js
index 188fc73..d3a85d2 100644
--- a/assets/people_sara-sunshine.md.ZW6v3r7F.lean.js
+++ b/assets/people_sara-sunshine.md.Mi-pXUXK.lean.js
@@ -1 +1 @@
-import{_ as e,c as s,o as a}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sara Sunshine","image":"/assets/people/sara-sunshine.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com//Sara-Sunshine","icon":"github"},{"link":"ssunshin@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sara-sunshine.html"}]]},"headers":[],"relativePath":"people/sara-sunshine.md","filePath":"people/sara-sunshine.md"}'),n={name:"people/sara-sunshine.md"};function o(t,r,i,l,c,p){return a(),s("div")}const d=e(n,[["render",o]]);export{u as __pageData,d as default};
+import{_ as e,c as s,o as a}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sara Sunshine","image":"/assets/people/sara-sunshine.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com//Sara-Sunshine","icon":"github"},{"link":"ssunshin@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sara-sunshine.html"}]]},"headers":[],"relativePath":"people/sara-sunshine.md","filePath":"people/sara-sunshine.md"}'),n={name:"people/sara-sunshine.md"};function o(t,r,i,l,c,p){return a(),s("div")}const d=e(n,[["render",o]]);export{u as __pageData,d as default};
diff --git a/assets/people_sheri-harari.md.Bkz3lxZL.js b/assets/people_sheri-harari.md.PzFaBhbu.js
similarity index 87%
rename from assets/people_sheri-harari.md.Bkz3lxZL.js
rename to assets/people_sheri-harari.md.PzFaBhbu.js
index e8fa46f..ae5b1e9 100644
--- a/assets/people_sheri-harari.md.Bkz3lxZL.js
+++ b/assets/people_sheri-harari.md.PzFaBhbu.js
@@ -1 +1 @@
-import{_ as e,c as a,o as i,b as r}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sheri Harari","image":"/assets/people/sheri-harari.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/SheriHarari","icon":"github"},{"link":"https://www.linkedin.com/in/sheri-harari-185615166/","icon":"linkedin"},{"link":"https://x.com/SheriHarari","icon":"twitter"},{"link":"sharari@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sheri-harari.html"}]]},"headers":[],"relativePath":"people/sheri-harari.md","filePath":"people/sheri-harari.md"}'),t={name:"people/sheri-harari.md"},o=r("p",null,"Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.",-1),s=[o];function n(l,h,c,p,d,m){return i(),a("div",null,s)}const g=e(t,[["render",n]]);export{u as __pageData,g as default};
+import{_ as e,c as a,o as i,b as r}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sheri Harari","image":"/assets/people/sheri-harari.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/SheriHarari","icon":"github"},{"link":"https://www.linkedin.com/in/sheri-harari-185615166/","icon":"linkedin"},{"link":"https://x.com/SheriHarari","icon":"twitter"},{"link":"sharari@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sheri-harari.html"}]]},"headers":[],"relativePath":"people/sheri-harari.md","filePath":"people/sheri-harari.md"}'),t={name:"people/sheri-harari.md"},o=r("p",null,"Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.",-1),s=[o];function n(l,h,c,p,d,m){return i(),a("div",null,s)}const g=e(t,[["render",n]]);export{u as __pageData,g as default};
diff --git a/assets/people_sheri-harari.md.Bkz3lxZL.lean.js b/assets/people_sheri-harari.md.PzFaBhbu.lean.js
similarity index 87%
rename from assets/people_sheri-harari.md.Bkz3lxZL.lean.js
rename to assets/people_sheri-harari.md.PzFaBhbu.lean.js
index e8fa46f..ae5b1e9 100644
--- a/assets/people_sheri-harari.md.Bkz3lxZL.lean.js
+++ b/assets/people_sheri-harari.md.PzFaBhbu.lean.js
@@ -1 +1 @@
-import{_ as e,c as a,o as i,b as r}from"./chunks/framework.B63u0Dcf.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sheri Harari","image":"/assets/people/sheri-harari.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/SheriHarari","icon":"github"},{"link":"https://www.linkedin.com/in/sheri-harari-185615166/","icon":"linkedin"},{"link":"https://x.com/SheriHarari","icon":"twitter"},{"link":"sharari@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sheri-harari.html"}]]},"headers":[],"relativePath":"people/sheri-harari.md","filePath":"people/sheri-harari.md"}'),t={name:"people/sheri-harari.md"},o=r("p",null,"Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.",-1),s=[o];function n(l,h,c,p,d,m){return i(),a("div",null,s)}const g=e(t,[["render",n]]);export{u as __pageData,g as default};
+import{_ as e,c as a,o as i,b as r}from"./chunks/framework.5XYse7Qj.js";const u=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Sheri Harari","image":"/assets/people/sheri-harari.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/SheriHarari","icon":"github"},{"link":"https://www.linkedin.com/in/sheri-harari-185615166/","icon":"linkedin"},{"link":"https://x.com/SheriHarari","icon":"twitter"},{"link":"sharari@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/sheri-harari.html"}]]},"headers":[],"relativePath":"people/sheri-harari.md","filePath":"people/sheri-harari.md"}'),t={name:"people/sheri-harari.md"},o=r("p",null,"Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.",-1),s=[o];function n(l,h,c,p,d,m){return i(),a("div",null,s)}const g=e(t,[["render",n]]);export{u as __pageData,g as default};
diff --git a/assets/people_teagan-mcmahon.md.uLB1lgiR.js b/assets/people_teagan-mcmahon.md.BizP6SUN.js
similarity index 91%
rename from assets/people_teagan-mcmahon.md.uLB1lgiR.js
rename to assets/people_teagan-mcmahon.md.BizP6SUN.js
index 2501a31..b26773d 100644
--- a/assets/people_teagan-mcmahon.md.uLB1lgiR.js
+++ b/assets/people_teagan-mcmahon.md.BizP6SUN.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t}from"./chunks/framework.B63u0Dcf.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.jpg","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"tmcmahon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/teagan-mcmahon.html"}]]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,m,r,h,i,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default};
+import{_ as e,c as a,o as t}from"./chunks/framework.5XYse7Qj.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.jpg","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"tmcmahon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/teagan-mcmahon.html"}]]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,m,r,h,i,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default};
diff --git a/assets/people_teagan-mcmahon.md.uLB1lgiR.lean.js b/assets/people_teagan-mcmahon.md.BizP6SUN.lean.js
similarity index 91%
rename from assets/people_teagan-mcmahon.md.uLB1lgiR.lean.js
rename to assets/people_teagan-mcmahon.md.BizP6SUN.lean.js
index 2501a31..b26773d 100644
--- a/assets/people_teagan-mcmahon.md.uLB1lgiR.lean.js
+++ b/assets/people_teagan-mcmahon.md.BizP6SUN.lean.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t}from"./chunks/framework.B63u0Dcf.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.jpg","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"tmcmahon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/teagan-mcmahon.html"}]]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,m,r,h,i,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default};
+import{_ as e,c as a,o as t}from"./chunks/framework.5XYse7Qj.js";const l=JSON.parse('{"title":"Research Technician","description":"","frontmatter":{"layout":"person","name":"Teagan McMahon","image":"/assets/people/teagan-mcmahon.jpg","title":"Research Technician","category":"Staff","links":[{"link":"https://github.com/tmcmaho","icon":"github"},{"link":"tmcmahon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/teagan-mcmahon.html"}]]},"headers":[],"relativePath":"people/teagan-mcmahon.md","filePath":"people/teagan-mcmahon.md"}'),n={name:"people/teagan-mcmahon.md"};function o(c,m,r,h,i,p){return t(),a("div")}const g=e(n,[["render",o]]);export{l as __pageData,g as default};
diff --git a/assets/people_tim-yu.md.5IvGg_B_.js b/assets/people_tim-yu.md.DR9R71qF.js
similarity index 85%
rename from assets/people_tim-yu.md.5IvGg_B_.js
rename to assets/people_tim-yu.md.DR9R71qF.js
index 261ad7f..5c3163c 100644
--- a/assets/people_tim-yu.md.5IvGg_B_.js
+++ b/assets/people_tim-yu.md.DR9R71qF.js
@@ -1 +1 @@
-import{_ as e,c as t,o as n,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/tim-yu.html"}]]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),l=[o];function s(u,c,p,r,m,d){return n(),t("div",null,l)}const f=e(i,[["render",s]]);export{_ as __pageData,f as default};
+import{_ as e,c as t,o as n,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/tim-yu.html"}]]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),l=[o];function s(u,c,p,r,m,d){return n(),t("div",null,l)}const f=e(i,[["render",s]]);export{_ as __pageData,f as default};
diff --git a/assets/people_tim-yu.md.5IvGg_B_.lean.js b/assets/people_tim-yu.md.DR9R71qF.lean.js
similarity index 85%
rename from assets/people_tim-yu.md.5IvGg_B_.lean.js
rename to assets/people_tim-yu.md.DR9R71qF.lean.js
index 261ad7f..5c3163c 100644
--- a/assets/people_tim-yu.md.5IvGg_B_.lean.js
+++ b/assets/people_tim-yu.md.DR9R71qF.lean.js
@@ -1 +1 @@
-import{_ as e,c as t,o as n,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/tim-yu.html"}]]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),l=[o];function s(u,c,p,r,m,d){return n(),t("div",null,l)}const f=e(i,[["render",s]]);export{_ as __pageData,f as default};
+import{_ as e,c as t,o as n,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Graduate Student","description":"","frontmatter":{"layout":"person","name":"Tim Yu","image":"/assets/people/tim-yu.jpg","title":"Graduate Student","category":"Grad Students","links":[{"link":"https://github.com/timcyu","icon":"github"},{"link":"https://www.linkedin.com/in/timyu316/","icon":"linkedin"},{"link":"timcyu@uw.edu","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/tim-yu.html"}]]},"headers":[],"relativePath":"people/tim-yu.md","filePath":"people/tim-yu.md"}'),i={name:"people/tim-yu.md"},o=a("p",null,"As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.",-1),l=[o];function s(u,c,p,r,m,d){return n(),t("div",null,l)}const f=e(i,[["render",s]]);export{_ as __pageData,f as default};
diff --git a/assets/people_wenlin-ren.md.BvOZ9g9J.js b/assets/people_wenlin-ren.md.BhY7Ucqw.js
similarity index 87%
rename from assets/people_wenlin-ren.md.BvOZ9g9J.js
rename to assets/people_wenlin-ren.md.BhY7Ucqw.js
index fce7dfe..cc314bd 100644
--- a/assets/people_wenlin-ren.md.BvOZ9g9J.js
+++ b/assets/people_wenlin-ren.md.BhY7Ucqw.js
@@ -1 +1 @@
-import{_ as e,c as n,o as t,b as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/wenlin-ren.html"}]]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,h,m){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default};
+import{_ as e,c as n,o as t,b as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/wenlin-ren.html"}]]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,h,m){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default};
diff --git a/assets/people_wenlin-ren.md.BvOZ9g9J.lean.js b/assets/people_wenlin-ren.md.BhY7Ucqw.lean.js
similarity index 87%
rename from assets/people_wenlin-ren.md.BvOZ9g9J.lean.js
rename to assets/people_wenlin-ren.md.BhY7Ucqw.lean.js
index fce7dfe..cc314bd 100644
--- a/assets/people_wenlin-ren.md.BvOZ9g9J.lean.js
+++ b/assets/people_wenlin-ren.md.BhY7Ucqw.lean.js
@@ -1 +1 @@
-import{_ as e,c as n,o as t,b as o}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/wenlin-ren.html"}]]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,h,m){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default};
+import{_ as e,c as n,o as t,b as o}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Wenlin Ren","image":"/assets/people/wenlin-ren.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/rwl18","icon":"github"},{"link":"https://www.linkedin.com/in/wenlin-ren/","icon":"linkedin"},{"link":"wren@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/wenlin-ren.html"}]]},"headers":[],"relativePath":"people/wenlin-ren.md","filePath":"people/wenlin-ren.md"}'),i={name:"people/wenlin-ren.md"},l=o("p",null,"Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.",-1),a=[l];function s(r,c,p,d,h,m){return t(),n("div",null,a)}const w=e(i,[["render",s]]);export{_ as __pageData,w as default};
diff --git a/assets/people_will-hannon.md.22MFpxTq.js b/assets/people_will-hannon.md.DJi2lHXj.js
similarity index 89%
rename from assets/people_will-hannon.md.22MFpxTq.js
rename to assets/people_will-hannon.md.DJi2lHXj.js
index fc7a72d..5cd301c 100644
--- a/assets/people_will-hannon.md.22MFpxTq.js
+++ b/assets/people_will-hannon.md.DJi2lHXj.js
@@ -1 +1 @@
-import{_ as n,c as e,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/will-hannon.html"}]]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default};
+import{_ as n,c as e,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/will-hannon.html"}]]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default};
diff --git a/assets/people_will-hannon.md.22MFpxTq.lean.js b/assets/people_will-hannon.md.DJi2lHXj.lean.js
similarity index 89%
rename from assets/people_will-hannon.md.22MFpxTq.lean.js
rename to assets/people_will-hannon.md.DJi2lHXj.lean.js
index fc7a72d..5cd301c 100644
--- a/assets/people_will-hannon.md.22MFpxTq.lean.js
+++ b/assets/people_will-hannon.md.DJi2lHXj.lean.js
@@ -1 +1 @@
-import{_ as n,c as e,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/will-hannon.html"}]]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default};
+import{_ as n,c as e,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const g=JSON.parse('{"title":"Data Scientist","description":"","frontmatter":{"layout":"person","name":"Will Hannon","image":"/assets/people/will-hannon.jpg","title":"Data Scientist","category":"Staff","links":[{"link":"https://github.com/WillHannon-MCB","icon":"github"},{"link":"https://www.linkedin.com/in/williamhannon/","icon":"linkedin"},{"link":"whannon@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/will-hannon.html"}]]},"headers":[],"relativePath":"people/will-hannon.md","filePath":"people/will-hannon.md"}'),i={name:"people/will-hannon.md"},o=a("p",null,"As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.",-1),l=[o];function s(r,c,p,d,h,m){return t(),e("div",null,l)}const _=n(i,[["render",s]]);export{g as __pageData,_ as default};
diff --git a/assets/people_xiaohui-ju.md.VZQuhgwu.js b/assets/people_xiaohui-ju.md.Dzqq7xVl.js
similarity index 87%
rename from assets/people_xiaohui-ju.md.VZQuhgwu.js
rename to assets/people_xiaohui-ju.md.Dzqq7xVl.js
index d45d7cc..5e02caf 100644
--- a/assets/people_xiaohui-ju.md.VZQuhgwu.js
+++ b/assets/people_xiaohui-ju.md.Dzqq7xVl.js
@@ -1 +1 @@
-import{_ as e,c as o,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/xiaohui-ju.html"}]]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),i={name:"people/xiaohui-ju.md"},n=a("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),l=[n];function s(r,c,u,p,h,d){return t(),o("div",null,l)}const x=e(i,[["render",s]]);export{_ as __pageData,x as default};
+import{_ as e,c as o,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/xiaohui-ju.html"}]]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),i={name:"people/xiaohui-ju.md"},n=a("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),l=[n];function s(r,c,u,p,h,d){return t(),o("div",null,l)}const x=e(i,[["render",s]]);export{_ as __pageData,x as default};
diff --git a/assets/people_xiaohui-ju.md.VZQuhgwu.lean.js b/assets/people_xiaohui-ju.md.Dzqq7xVl.lean.js
similarity index 87%
rename from assets/people_xiaohui-ju.md.VZQuhgwu.lean.js
rename to assets/people_xiaohui-ju.md.Dzqq7xVl.lean.js
index d45d7cc..5e02caf 100644
--- a/assets/people_xiaohui-ju.md.VZQuhgwu.lean.js
+++ b/assets/people_xiaohui-ju.md.Dzqq7xVl.lean.js
@@ -1 +1 @@
-import{_ as e,c as o,o as t,b as a}from"./chunks/framework.B63u0Dcf.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/xiaohui-ju.html"}]]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),i={name:"people/xiaohui-ju.md"},n=a("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),l=[n];function s(r,c,u,p,h,d){return t(),o("div",null,l)}const x=e(i,[["render",s]]);export{_ as __pageData,x as default};
+import{_ as e,c as o,o as t,b as a}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"Postdoctoral Fellow","description":"","frontmatter":{"layout":"person","name":"Xiaohui Ju","image":"/assets/people/xiaohui-ju.jpg","title":"Postdoctoral Fellow","category":"Postdocs","links":[{"link":"https://github.com/juxh23","icon":"github"},{"link":"https://www.linkedin.com/in/xiaohui-ju-13b4912a7","icon":"linkedin"},{"link":"xju@fredhutch.org","icon":"email"}],"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/people/xiaohui-ju.html"}]]},"headers":[],"relativePath":"people/xiaohui-ju.md","filePath":"people/xiaohui-ju.md"}'),i={name:"people/xiaohui-ju.md"},n=a("p",null,"As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.",-1),l=[n];function s(r,c,u,p,h,d){return t(),o("div",null,l)}const x=e(i,[["render",s]]);export{_ as __pageData,x as default};
diff --git a/assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.js b/assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.js
new file mode 100644
index 0000000..f36a276
--- /dev/null
+++ b/assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.js
@@ -0,0 +1 @@
+import{_ as e,c as a,o as t,f as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.5XYse7Qj.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/2024-05-25_h5-dms.html"}]]},"headers":[],"relativePath":"posts/2024-05-25_h5-dms.md","filePath":"posts/2024-05-25_h5-dms.md"}'),u={name:"posts/2024-05-25_h5-dms.md"},m=s('<p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>H5 influenza from clade 2.3.4.4b <a href="https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article" target="_blank" rel="noreferrer">has been causing</a> outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.</p><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study led by Bernadeta Dadonaite</a>, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.</p><p><img src="'+r+'" alt="molecular phenotypes measured"></p><p>To make these measurements safely, we used a previously described <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus deep mutational scanning system</a> that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.</p><p><img src="'+i+'" alt="pseudovirus schematic"></p><p>First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.</p><p><img src="'+n+'" alt="cell entry heatmap"><img src="'+o+'" alt="cell entry structure"></p><p>Next we measured how mutations affect HA&#39;s ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:</p><p><img src="'+l+'" alt="a2-6 usage"></p><p>We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:</p><p><img src="'+h+'" alt="stability"></p><p>Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:</p><p><img src="'+c+'" alt="escape"></p><p>To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see <a href="https://nextstrain.org/groups/moncla-lab/h5nx/2024-05-25_h5-dms/clade-2344b" target="_blank" rel="noreferrer">here</a> to color a phylogenetic tree by the measured phenotypes).</p><p>Angie Hinrichs <a href="https://x.com/AngieSHinrichs/status/1804270714570313873" target="_blank" rel="noreferrer">has also integrated the data into the UShER H5 trees</a>.</p><h2 id="how-to-visualize-and-access-the-data" tabindex="-1">How to visualize and access the data <a class="header-anchor" href="#how-to-visualize-and-access-the-data" aria-label="Permalink to &quot;How to visualize and access the data&quot;">​</a></h2><p>To make the data as accessible as possible for use by others, see</p><ul><li><p>An <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">interactive page</a> that allows you to visually examine heatmaps showing the effects of all the mutations on each measured phenotype.</p></li><li><p>An <a href="https://dms-viz.github.io/v0/?data=https%3A%2F%2Fraw.githubusercontent.com%2Fdms-vep%2FFlu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS%2Fmain%2Fresults%2Fdms-viz%2Fdms-viz.json" target="_blank" rel="noreferrer">interactive structure-based visualization</a></p></li><li><p>The <a href="https://github.com/dms-vep/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/blob/main/results/summaries/phenotypes.csv" target="_blank" rel="noreferrer">numerical values of the measurements</a> available.</p></li><li><p>Note that there are multiple HA numbering schemes in use, so make sure <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/numbering.html" target="_blank" rel="noreferrer">you understand how the mutations are being numbered</a>.</p></li></ul><h2 id="see-also" tabindex="-1">See also <a class="header-anchor" href="#see-also" aria-label="Permalink to &quot;See also&quot;">​</a></h2><p>See also <a href="https://x.com/jbloom_lab/status/1794364494858346803" target="_blank" rel="noreferrer">Jesse&#39;s Twitter thread</a> and <a href="https://slides.com/jbloom/h5-dms-short" target="_blank" rel="noreferrer">some slides about the study</a>.</p>',23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default};
diff --git a/assets/posts_h5-dms.md.VmjcEWBz.lean.js b/assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.lean.js
similarity index 51%
rename from assets/posts_h5-dms.md.VmjcEWBz.lean.js
rename to assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.lean.js
index 0a3c013..783f7f9 100644
--- a/assets/posts_h5-dms.md.VmjcEWBz.lean.js
+++ b/assets/posts_2024-05-25_h5-dms.md.n9FKwTAN.lean.js
@@ -1 +1 @@
-import{_ as e,c as a,o as t,f as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.B63u0Dcf.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/h5-dms.html"}]]},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s("",23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default};
+import{_ as e,c as a,o as t,f as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.5XYse7Qj.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/2024-05-25_h5-dms.html"}]]},"headers":[],"relativePath":"posts/2024-05-25_h5-dms.md","filePath":"posts/2024-05-25_h5-dms.md"}'),u={name:"posts/2024-05-25_h5-dms.md"},m=s("",23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default};
diff --git a/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.js b/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.js
new file mode 100644
index 0000000..296c210
--- /dev/null
+++ b/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.js
@@ -0,0 +1 @@
+import{_ as e,c as a,o as t,f as r,S as i,U as s,V as n,W as o,X as l,Y as u,Z as p,$ as h,a0 as c}from"./chunks/framework.5XYse7Qj.js";const k=JSON.parse('{"title":"Sequencing-based neutralization assays for influenza","description":"","frontmatter":{"layout":"post","title":"Sequencing-based neutralization assays for influenza","date":"2024-09-24T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/2024-09-24_flu_seqneut.html"}]]},"headers":[],"relativePath":"posts/2024-09-24_flu_seqneut.md","filePath":"posts/2024-09-24_flu_seqneut.md"}'),d={name:"posts/2024-09-24_flu_seqneut.md"},f=r('<p>In <a href="https://doi.org/10.1128/jvi.00689-24" target="_blank" rel="noreferrer">a paper</a> just published in <em>Journal of Virology</em>, we describe a new sequencing-based neutralization assay that dramatically increases the scale at which it is possible to measure how sera or antibodies neutralize different influenza virus strains.</p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>Neutralization assays are central to studying viral immunity. These assays involve making dilutions of serum, adding virus and cells, and then quantifying how much each serum dilution inhibits viral infection. The traditional readout is GFP fluorescence, luciferase, or plaques. Such readouts allow one virus to be analyzed per row or column of a 96-well plate, meaning that a single plate can be used to measure titers for at most 8 to 12 different serum-virus pairs. This limited throughput is a real problem when studying an antigenically variable virus like influenza, where we may want know neutralization titers against dozens or even hundreds of different viral strains.</p><p><a href="https://doi.org/10.1128/jvi.00689-24" target="_blank" rel="noreferrer">Our paper</a> describes a new approach spearheaded by Andrea Loes in our group that can measure titers for hundreds (or even up to a thousand) serum-virus pairs per 96-well plate, as shown below.</p><p><img src="'+i+'" alt="measurements per plate"></p><p>How do we do this? The essence of our approach is to barcode each influenza virus strain, then combine all of the viruses and read out neutralization by all the viruses at once by deep sequencing, as schematized below. So it&#39;s like a traditional neutralization assay, except we measure all the viruses at once, rather than one at a time.</p><p><img src="'+s+'" alt="schematic of sequencing-based neutralization"></p><p>Below are some representative neutralization curves from the sequencing-based assay. They are identical to curves from traditional one-virus versus one-serum assays: the only difference is we generate replicate curves for hundreds of serum-virus pairs on each plate, rather than just a few curves per plate.</p><p><img src="'+n+'" alt="example sequencing-based neutralization curves"></p><p>The neutralization titers measured using the sequencing-based assay are highly reproducible both across replicate barcodes for the same virus on the same plate, and across different plates run on different days, as shown below.</p><p><img src="'+o+'" alt="correlations within assay"></p><p>The neutralization curves measured using the sequencing-based assay are also indistinguishable from those measured using a traditional fluorescence-based assay, as shown below:</p><p><img src="'+l+'" alt="correlations with traditional"></p><p>We applied the assay to examine the response to repeated influenza vaccination, an important topic as <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00266-1/fulltext" target="_blank" rel="noreferrer">some studies</a> suggest reduced effectiveness of repeated vaccination. We analyzed samples from the <a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae380/7718587" target="_blank" rel="noreferrer">DRIVE study</a> led by Ben Cowling and Sarah Cobey. For each study participant at each timepoint, we used the sequencing-based neutralization assay to measure titers against 36 H1N1 strains (five vaccine strains plus 31 recent strains). So for each participant, we generate data like that shown below, which quantifies the pre- and post-vaccination titers against a wide range of recent viral strains.</p><p><img src="'+u+'" alt="example neutralization landscapes"></p><p>In our sub-study (we only examined a fraction of all of the DRIVE samples), we looked at the response to the 2021-2022 vaccine in individual who had or had not been vaccinated in the prior year (2020-2021). Individuals who had <strong>not</strong> been vaccinated in the prior year (2020-2021) started with much lower pre-vaccination titers (purple points), but had a substantially larger marginal increase in titers after vaccination in 2021-2022 (red and green points) than individuals who had also been vaccinated the prior year. (This sort of makes sense: their starting titers were lower so there was more of an increase after vaccination.) The titers for the two groups are shown below:</p><p><img src="'+p+'" alt="vaccine response"></p><p>However, despite the larger marginal increase in titers for participants without prior-year vaccination, the final titers (especially at day 182) were similar among participants with and without a prior-year vaccination, since prior-year vaccinees started with higher titers.</p><p><img src="'+h+'" alt="final titers"></p><p>Importantly, the participant-average plots above mask person- and virus-specific variation that probably has important implications for both influenza evolution and disease susceptibility (see plot below). Indeed, one of the things we are most excited about is using this new assay to extensively probe person-to-person variation in titers to different viral strains.</p><p><img src="'+c+'" alt="variation among viruses and individuals"></p><h2 id="want-to-use-this-approach-for-your-own-studies" tabindex="-1">Want to use this approach for your own studies? <a class="header-anchor" href="#want-to-use-this-approach-for-your-own-studies" aria-label="Permalink to &quot;Want to use this approach for your own studies?&quot;">​</a></h2><p>We think sequencing-based neutralization assays could be useful for a wide range of studies. To make the approach as accessible as possible for others, we have created:</p><ul><li><p>A publicly available <a href="https://github.com/jbloomlab/seqneut-pipeline" target="_blank" rel="noreferrer">computational pipeline</a> to analyze sequencing-based neutralization assay data. Note that this pipeline leverages an early <a href="https://jbloomlab.github.io/neutcurve/" target="_blank" rel="noreferrer">Python package we developed to fit neutralization curves</a>; the ability to automate the curve fitting becomes important when you are trying to analyze thousands of neutralization curves per week!</p></li><li><p>A publicly available detailed <a href="https://doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1" target="_blank" rel="noreferrer">experimental protocol</a>.</p></li></ul><p>We already have scientists from several different research groups scheduled to visit our lab in the coming months to learn the assay; please reach out if you are interested in trying it yourself!</p><h2 id="what-s-next" tabindex="-1">What&#39;s next? <a class="header-anchor" href="#what-s-next" aria-label="Permalink to &quot;What&#39;s next?&quot;">​</a></h2><p>Our lab has already extended this assay to measure ~10,000 neutralization titers of human sera against recent H3N2 strains, and we are hopeful these data can eventually be used to understand which influenza strains are evolutionarily successful, thereby helping with vaccine-strain selection. Stay tuned for more on this soon!</p><p>Also, feel free to reach out if you are interested in using the large sets of neutralization titers for evolutionarily or epidemiological modeling. All the raw data from the study described above is <a href="https://github.com/jbloomlab/flu_seqneut_pdmH1N1_2023-2024" target="_blank" rel="noreferrer">publicly available</a>; we&#39;re also happy to share interim data from our in-progress studies that we haven&#39;t yet pre-printed or published.</p>',29),m=[f];function b(v,g,w,y,_,z){return t(),a("div",null,m)}const x=e(d,[["render",b]]);export{k as __pageData,x as default};
diff --git a/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.lean.js b/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.lean.js
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+++ b/assets/posts_2024-09-24_flu_seqneut.md.Od5R4u5y.lean.js
@@ -0,0 +1 @@
+import{_ as e,c as a,o as t,f as r,S as i,U as s,V as n,W as o,X as l,Y as u,Z as p,$ as h,a0 as c}from"./chunks/framework.5XYse7Qj.js";const k=JSON.parse('{"title":"Sequencing-based neutralization assays for influenza","description":"","frontmatter":{"layout":"post","title":"Sequencing-based neutralization assays for influenza","date":"2024-09-24T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/2024-09-24_flu_seqneut.html"}]]},"headers":[],"relativePath":"posts/2024-09-24_flu_seqneut.md","filePath":"posts/2024-09-24_flu_seqneut.md"}'),d={name:"posts/2024-09-24_flu_seqneut.md"},f=r("",29),m=[f];function b(v,g,w,y,_,z){return t(),a("div",null,m)}const x=e(d,[["render",b]]);export{k as __pageData,x as default};
diff --git a/assets/posts_h5-dms.md.VmjcEWBz.js b/assets/posts_h5-dms.md.VmjcEWBz.js
deleted file mode 100644
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--- a/assets/posts_h5-dms.md.VmjcEWBz.js
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-import{_ as e,c as a,o as t,f as s,L as r,M as i,N as n,O as o,P as l,Q as h,R as c}from"./chunks/framework.B63u0Dcf.js";const H=JSON.parse('{"title":"Deep mutational scanning of H5 influenza hemagglutinin","description":"","frontmatter":{"layout":"post","title":"Deep mutational scanning of H5 influenza hemagglutinin","date":"2024-05-25T00:00:00.000Z","author":"Jesse Bloom","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/posts/h5-dms.html"}]]},"headers":[],"relativePath":"posts/h5-dms.md","filePath":"posts/h5-dms.md"}'),u={name:"posts/h5-dms.md"},m=s('<p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>H5 influenza from clade 2.3.4.4b <a href="https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article" target="_blank" rel="noreferrer">has been causing</a> outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.</p><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study led by Bernadeta Dadonaite</a>, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.</p><p><img src="'+r+'" alt="molecular phenotypes measured"></p><p>To make these measurements safely, we used a previously described <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus deep mutational scanning system</a> that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.</p><p><img src="'+i+'" alt="pseudovirus schematic"></p><p>First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.</p><p><img src="'+n+'" alt="cell entry heatmap"><img src="'+o+'" alt="cell entry structure"></p><p>Next we measured how mutations affect HA&#39;s ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:</p><p><img src="'+l+'" alt="a2-6 usage"></p><p>We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:</p><p><img src="'+h+'" alt="stability"></p><p>Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:</p><p><img src="'+c+'" alt="escape"></p><p>To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see <a href="https://nextstrain.org/groups/moncla-lab/h5nx/h5-dms/clade-2344b" target="_blank" rel="noreferrer">here</a> to color a phylogenetic tree by the measured phenotypes).</p><p>Angie Hinrichs <a href="https://x.com/AngieSHinrichs/status/1804270714570313873" target="_blank" rel="noreferrer">has also integrated the data into the UShER H5 trees</a>.</p><h2 id="how-to-visualize-and-access-the-data" tabindex="-1">How to visualize and access the data <a class="header-anchor" href="#how-to-visualize-and-access-the-data" aria-label="Permalink to &quot;How to visualize and access the data&quot;">​</a></h2><p>To make the data as accessible as possible for use by others, see</p><ul><li><p>An <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">interactive page</a> that allows you to visually examine heatmaps showing the effects of all the mutations on each measured phenotype.</p></li><li><p>An <a href="https://dms-viz.github.io/v0/?data=https%3A%2F%2Fraw.githubusercontent.com%2Fdms-vep%2FFlu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS%2Fmain%2Fresults%2Fdms-viz%2Fdms-viz.json" target="_blank" rel="noreferrer">interactive structure-based visualization</a></p></li><li><p>The <a href="https://github.com/dms-vep/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/blob/main/results/summaries/phenotypes.csv" target="_blank" rel="noreferrer">numerical values of the measurements</a> available.</p></li><li><p>Note that there are multiple HA numbering schemes in use, so make sure <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/numbering.html" target="_blank" rel="noreferrer">you understand how the mutations are being numbered</a>.</p></li></ul><h2 id="see-also" tabindex="-1">See also <a class="header-anchor" href="#see-also" aria-label="Permalink to &quot;See also&quot;">​</a></h2><p>See also <a href="https://x.com/jbloom_lab/status/1794364494858346803" target="_blank" rel="noreferrer">Jesse&#39;s Twitter thread</a> and <a href="https://slides.com/jbloom/h5-dms-short" target="_blank" rel="noreferrer">some slides about the study</a>.</p>',23),d=[m];function p(f,_,g,b,v,y){return t(),a("div",null,d)}const k=e(u,[["render",p]]);export{H as __pageData,k as default};
diff --git a/assets/posts_index.md.CJoAjt6O.js b/assets/posts_index.md.BHY75z0K.js
similarity index 84%
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+++ b/assets/posts_index.md.BHY75z0K.js
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diff --git a/assets/posts_index.md.CJoAjt6O.lean.js b/assets/posts_index.md.BHY75z0K.lean.js
similarity index 84%
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diff --git a/assets/projects_alignparse.md.C5_09-UH.js b/assets/projects_alignparse.md.Cu19yJSH.js
similarity index 92%
rename from assets/projects_alignparse.md.C5_09-UH.js
rename to assets/projects_alignparse.md.Cu19yJSH.js
index 5fad447..8604931 100644
--- a/assets/projects_alignparse.md.C5_09-UH.js
+++ b/assets/projects_alignparse.md.Cu19yJSH.js
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+import{_ as a,c as t,o,b as e}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"alignparse","link":"https://jbloomlab.github.io/alignparse/","github":"https://github.com/jbloomlab/alignparse","documentation":"https://jbloomlab.github.io/alignparse/","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/projects/alignparse.html"}]]},"headers":[],"relativePath":"projects/alignparse.md","filePath":"projects/alignparse.md"}'),s={name:"projects/alignparse.md"},n=e("p",null,"Python package to parse complex user-defined features from long-read PacBio sequencing.",-1),r=e("hr",null,null,-1),l=[n,r];function i(p,c,h,d,m,g){return o(),t("div",null,l)}const b=a(s,[["render",i]]);export{_ as __pageData,b as default};
diff --git a/assets/projects_alignparse.md.C5_09-UH.lean.js b/assets/projects_alignparse.md.Cu19yJSH.lean.js
similarity index 92%
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rename to assets/projects_alignparse.md.Cu19yJSH.lean.js
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+import{_ as a,c as t,o,b as e}from"./chunks/framework.5XYse7Qj.js";const _=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"alignparse","link":"https://jbloomlab.github.io/alignparse/","github":"https://github.com/jbloomlab/alignparse","documentation":"https://jbloomlab.github.io/alignparse/","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/projects/alignparse.html"}]]},"headers":[],"relativePath":"projects/alignparse.md","filePath":"projects/alignparse.md"}'),s={name:"projects/alignparse.md"},n=e("p",null,"Python package to parse complex user-defined features from long-read PacBio sequencing.",-1),r=e("hr",null,null,-1),l=[n,r];function i(p,c,h,d,m,g){return o(),t("div",null,l)}const b=a(s,[["render",i]]);export{_ as __pageData,b as default};
diff --git a/assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.js b/assets/projects_dms-vep-pipeline-3.md.BJYuQsSn.js
similarity index 85%
rename from assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.js
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index eb0c4a5..2d2a733 100644
--- a/assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.js
+++ b/assets/projects_dms-vep-pipeline-3.md.BJYuQsSn.js
@@ -1 +1 @@
-import{_ as t,c as p,o as n,b as e}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"dms-vep-pipeline-3","link":"https://github.com/dms-vep/dms-vep-pipeline-3","github":"https://github.com/dms-vep/dms-vep-pipeline-3","documentation":"https://github.com/dms-vep/dms-vep-pipeline-3","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/projects/dms-vep-pipeline-3.html"}]]},"headers":[],"relativePath":"projects/dms-vep-pipeline-3.md","filePath":"projects/dms-vep-pipeline-3.md"}'),i={name:"projects/dms-vep-pipeline-3.md"},s=e("p",null,"Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.",-1),o=e("hr",null,null,-1),a=[s,o];function l(r,c,d,m,h,_){return n(),p("div",null,a)}const f=t(i,[["render",l]]);export{v as __pageData,f as default};
+import{_ as t,c as p,o as n,b as e}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"","description":"","frontmatter":{"layout":"project","name":"dms-vep-pipeline-3","link":"https://github.com/dms-vep/dms-vep-pipeline-3","github":"https://github.com/dms-vep/dms-vep-pipeline-3","documentation":"https://github.com/dms-vep/dms-vep-pipeline-3","head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/projects/dms-vep-pipeline-3.html"}]]},"headers":[],"relativePath":"projects/dms-vep-pipeline-3.md","filePath":"projects/dms-vep-pipeline-3.md"}'),i={name:"projects/dms-vep-pipeline-3.md"},s=e("p",null,"Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.",-1),o=e("hr",null,null,-1),a=[s,o];function l(r,c,d,m,h,_){return n(),p("div",null,a)}const f=t(i,[["render",l]]);export{v as __pageData,f as default};
diff --git a/assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.lean.js b/assets/projects_dms-vep-pipeline-3.md.BJYuQsSn.lean.js
similarity index 85%
rename from assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.lean.js
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index eb0c4a5..2d2a733 100644
--- a/assets/projects_dms-vep-pipeline-3.md.BEZzUcEh.lean.js
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diff --git a/assets/research_index.md.DvMafqPA.js b/assets/research_index.md.BjbpOyS6.js
similarity index 85%
rename from assets/research_index.md.DvMafqPA.js
rename to assets/research_index.md.BjbpOyS6.js
index 19dcbcf..0717fd6 100644
--- a/assets/research_index.md.DvMafqPA.js
+++ b/assets/research_index.md.BjbpOyS6.js
@@ -1 +1 @@
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+import{_ as e,c as r,o as a}from"./chunks/framework.5XYse7Qj.js";const p=JSON.parse('{"title":"","description":"","frontmatter":{"research":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/research/"}]]},"headers":[],"relativePath":"research/index.md","filePath":"research/index.md"}'),t={name:"research/index.md"};function c(n,s,o,i,d,h){return a(),r("div")}const _=e(t,[["render",c]]);export{p as __pageData,_ as default};
diff --git a/assets/research_index.md.DvMafqPA.lean.js b/assets/research_index.md.BjbpOyS6.lean.js
similarity index 85%
rename from assets/research_index.md.DvMafqPA.lean.js
rename to assets/research_index.md.BjbpOyS6.lean.js
index 19dcbcf..0717fd6 100644
--- a/assets/research_index.md.DvMafqPA.lean.js
+++ b/assets/research_index.md.BjbpOyS6.lean.js
@@ -1 +1 @@
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+import{_ as e,c as r,o as a}from"./chunks/framework.5XYse7Qj.js";const p=JSON.parse('{"title":"","description":"","frontmatter":{"research":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/research/"}]]},"headers":[],"relativePath":"research/index.md","filePath":"research/index.md"}'),t={name:"research/index.md"};function c(n,s,o,i,d,h){return a(),r("div")}const _=e(t,[["render",c]]);export{p as __pageData,_ as default};
diff --git a/assets/research_research-aims.md.48uPTPik.js b/assets/research_research-aims.md.48uPTPik.js
deleted file mode 100644
index 395c974..0000000
--- a/assets/research_research-aims.md.48uPTPik.js
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-import{_ as e,c as a,o as t,f as r,S as i,U as n}from"./chunks/framework.B63u0Dcf.js";const v=JSON.parse('{"title":"Our Research","description":"","frontmatter":{"title":"Our Research","isAim":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/research/research-aims.html"}]]},"headers":[],"relativePath":"research/research-aims.md","filePath":"research/research-aims.md"}'),o={name:"research/research-aims.md"},s=r('<h2 id="deep-mutational-scanning" tabindex="-1">Deep Mutational Scanning <a class="header-anchor" href="#deep-mutational-scanning" aria-label="Permalink to &quot;Deep Mutational Scanning&quot;">​</a></h2><p>Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.</p><p><img src="'+i+'" alt="&quot;Pseudovirus neutralization system&quot;"></p><p>We primarily perform these experiments using a <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus system</a> that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">SARS-CoV-2 spike</a>, <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">influenza hemagglutinin</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1074761324003194" target="_blank" rel="noreferrer">Lassa virus GPC</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1931312823002184" target="_blank" rel="noreferrer">HIV envelope</a>, and <a href="https://doi.org/10.1101/2024.04.17.589977" target="_blank" rel="noreferrer">Nipah virus RBP</a>.</p><p>Deep mutational scanning can inform efforts to <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">forecast the evolution of human seasonal viruses</a> and <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">surveil the evolution of potential pandemic viruses</a>. To facilitate the use of deep mutational scanning for these important goals, we develop <a href="https://dms-viz.github.io/" target="_blank" rel="noreferrer">interactive visualization tools</a> and <a href="https://github.com/dms-vep/dms-vep-pipeline-3" target="_blank" rel="noreferrer">data analysis pipelines</a>. See <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">here</a> for an example of how we analyze and visualize large datasets to inform the study of viral evolution.</p><h2 id="interplay-of-immunity-and-viral-evolution" tabindex="-1">Interplay of Immunity and Viral Evolution <a class="header-anchor" href="#interplay-of-immunity-and-viral-evolution" aria-label="Permalink to &quot;Interplay of Immunity and Viral Evolution&quot;">​</a></h2><p>We study immunity and viral evolution at both the population and single-cell levels.</p><p><img src="'+n+'" alt="&quot;Sequencing-based neutralization assay&quot;"></p><p>At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both <a href="https://www.sciencedirect.com/science/article/pii/S1931312824002336" target="_blank" rel="noreferrer">deep mutational scanning</a> and a <a href="https://doi.org/10.1101/2024.03.08.584176" target="_blank" rel="noreferrer">sequencing based-neutralization assay</a> we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).</p><p>At the single-cell level, we developed approaches to <a href="https://journals.asm.org/doi/10.1128/jvi.00500-19" target="_blank" rel="noreferrer">sequence viruses in single cells</a> and <a href="https://elifesciences.org/articles/86852" target="_blank" rel="noreferrer">quantify how many progeny each infected cell produces</a>. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.</p><h2 id="big-datasets-and-viral-evolution" tabindex="-1">Big Datasets and Viral Evolution <a class="header-anchor" href="#big-datasets-and-viral-evolution" aria-label="Permalink to &quot;Big Datasets and Viral Evolution&quot;">​</a></h2><p>We also develop new ways to leverage large datasets to better understand viral evolution.</p><p>We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see <a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank" rel="noreferrer">this paper</a> and <a href="https://slides.com/jbloom/sars2-mut-fitness/" target="_blank" rel="noreferrer">these slides</a>). We&#39;ve also created a platform to <a href="https://jbloomlab.github.io/SARS2-mut-fitness/" target="_blank" rel="noreferrer">visualize the mutational effects</a> to aid in interpretation of viral evolution.</p><p>We have also integrated thousands of deep mutational scanning measurements into an <a href="https://jbloomlab.github.io/SARS2-RBD-escape-calc/" target="_blank" rel="noreferrer">antibody-escape calculator</a> that was <a href="https://slides.com/jbloom/sars2-rbd-escape-calc#/12" target="_blank" rel="noreferrer">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p><p>We also have projects that involve analyzing the evolution of viruses <a href="https://elifesciences.org/articles/26875" target="_blank" rel="noreferrer">within individual infected humans</a>, and developing models to <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank" rel="noreferrer">understand epistasis among viral mutations</a>.</p>',15),l=[s];function c(p,u,h,d,f,m){return t(),a("div",null,l)}const _=e(o,[["render",c]]);export{v as __pageData,_ as default};
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new file mode 100644
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+import{_ as e,c as a,o as t,f as r,a1 as i,a2 as n}from"./chunks/framework.5XYse7Qj.js";const v=JSON.parse('{"title":"Our Research","description":"","frontmatter":{"title":"Our Research","isAim":true,"head":[["link",{"rel":"canonical","href":"https://jbloomlab.org/research/research-aims.html"}]]},"headers":[],"relativePath":"research/research-aims.md","filePath":"research/research-aims.md"}'),o={name:"research/research-aims.md"},s=r('<h2 id="deep-mutational-scanning" tabindex="-1">Deep Mutational Scanning <a class="header-anchor" href="#deep-mutational-scanning" aria-label="Permalink to &quot;Deep Mutational Scanning&quot;">​</a></h2><p>Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.</p><p><img src="'+i+'" alt="&quot;Pseudovirus neutralization system&quot;"></p><p>We primarily perform these experiments using a <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus system</a> that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">SARS-CoV-2 spike</a>, <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">influenza hemagglutinin</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1074761324003194" target="_blank" rel="noreferrer">Lassa virus GPC</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1931312823002184" target="_blank" rel="noreferrer">HIV envelope</a>, and <a href="https://doi.org/10.1101/2024.04.17.589977" target="_blank" rel="noreferrer">Nipah virus RBP</a>.</p><p>Deep mutational scanning can inform efforts to <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">forecast the evolution of human seasonal viruses</a> and <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">surveil the evolution of potential pandemic viruses</a>. To facilitate the use of deep mutational scanning for these important goals, we develop <a href="https://dms-viz.github.io/" target="_blank" rel="noreferrer">interactive visualization tools</a> and <a href="https://github.com/dms-vep/dms-vep-pipeline-3" target="_blank" rel="noreferrer">data analysis pipelines</a>. See <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">here</a> for an example of how we analyze and visualize large datasets to inform the study of viral evolution.</p><h2 id="interplay-of-immunity-and-viral-evolution" tabindex="-1">Interplay of Immunity and Viral Evolution <a class="header-anchor" href="#interplay-of-immunity-and-viral-evolution" aria-label="Permalink to &quot;Interplay of Immunity and Viral Evolution&quot;">​</a></h2><p>We study immunity and viral evolution at both the population and single-cell levels.</p><p><img src="'+n+'" alt="&quot;Sequencing-based neutralization assay&quot;"></p><p>At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both <a href="https://www.sciencedirect.com/science/article/pii/S1931312824002336" target="_blank" rel="noreferrer">deep mutational scanning</a> and a <a href="https://doi.org/10.1101/2024.03.08.584176" target="_blank" rel="noreferrer">sequencing based-neutralization assay</a> we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).</p><p>At the single-cell level, we developed approaches to <a href="https://journals.asm.org/doi/10.1128/jvi.00500-19" target="_blank" rel="noreferrer">sequence viruses in single cells</a> and <a href="https://elifesciences.org/articles/86852" target="_blank" rel="noreferrer">quantify how many progeny each infected cell produces</a>. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.</p><h2 id="big-datasets-and-viral-evolution" tabindex="-1">Big Datasets and Viral Evolution <a class="header-anchor" href="#big-datasets-and-viral-evolution" aria-label="Permalink to &quot;Big Datasets and Viral Evolution&quot;">​</a></h2><p>We also develop new ways to leverage large datasets to better understand viral evolution.</p><p>We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see <a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank" rel="noreferrer">this paper</a> and <a href="https://slides.com/jbloom/sars2-mut-fitness/" target="_blank" rel="noreferrer">these slides</a>). We&#39;ve also created a platform to <a href="https://jbloomlab.github.io/SARS2-mut-fitness/" target="_blank" rel="noreferrer">visualize the mutational effects</a> to aid in interpretation of viral evolution.</p><p>We have also integrated thousands of deep mutational scanning measurements into an <a href="https://jbloomlab.github.io/SARS2-RBD-escape-calc/" target="_blank" rel="noreferrer">antibody-escape calculator</a> that was <a href="https://slides.com/jbloom/sars2-rbd-escape-calc#/12" target="_blank" rel="noreferrer">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p><p>We also have projects that involve analyzing the evolution of viruses <a href="https://elifesciences.org/articles/26875" target="_blank" rel="noreferrer">within individual infected humans</a>, and developing models to <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank" rel="noreferrer">understand epistasis among viral mutations</a>.</p>',15),l=[s];function c(p,u,h,d,f,m){return t(),a("div",null,l)}const _=e(o,[["render",c]]);export{v as __pageData,_ as default};
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="mx-auto max-w-4xl px-4 text-left flex flex-col" data-v-ff69af82><div class="flex-grow" data-v-ff69af82><h1 class="text-4xl sm:text-5xl md:text-7xl lg:text-8xl text-gray-800 select-none" data-v-ff69af82> Welcome to the <span class="block font-bold" data-v-ff69af82>Bloom Lab</span></h1><p class="text-xl md:text-2xl lg:text-3xl text-gray-600 mt-2 lg:mt-4 select-none" data-v-ff69af82> where we study the evolution of <span class="italic" style="color:#000000;background-color:rgba(0, 0, 0, 0.1);" data-v-ff69af82>Viruses</span></p><p class="text-sm md:text-base lg:text-lg text-gray-500 mt-4 md:mt-6 lg:mt-12" data-v-ff69af82> In the <strong data-v-ff69af82>Bloom lab</strong>, we study the evolution of viruses and proteins. We use experimental and computational techniques to understand the molecular constraints on viral proteins, and how these constraints shape the capacity of viruses to evolve to escape antibodies, erode pre-existing immunity, and adapt to new hosts. </p><p class="text-sm md:text-base lg:text-lg text-gray-500 mt-2 md:mt-4 lg:mt-6" data-v-ff69af82> Our lab is part of the <a href="https://www.fredhutch.org/en/research/divisions/basic-sciences-division.html" data-v-ff69af82>Basic Sciences Divison</a> and the <a href="https://www.fredhutch.org/en/research/divisions/public-health-sciences-division/research/computational-biology.html" data-v-ff69af82>Computational Biology Program</a> at the Fred Hutch. We are also affiliated with the <a href="https://www.gs.washington.edu/" data-v-ff69af82>Genome Sciences</a> and <a href="https://microbiology.washington.edu/uw-microbiology-home" data-v-ff69af82>Microbiology</a> Departments at the University of Washington, and graduate students often join our lab through the <a href="https://mcb-seattle.edu" data-v-ff69af82>MCB program</a>. Jesse Bloom is an Investigator of the <a href="https://www.hhmi.org/research" data-v-ff69af82>Howard Hughes Medical Institute</a>. </p></div><div class="text-center mt-8 md:mt-12 mb-2" data-v-ff69af82><a href="/research/" class="no-underline text-gray-600 hover:text-gray-600 hover:shadow-md hover:shadow-custom-orange rounded-lg bg-custom-soft p-2 overflow-hidden transition-shadow duration-200 ease-in-out text-sm md:text-base lg:text-lg" data-v-ff69af82>Learn more about our research</a></div></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PNAS</span><span class="pl-3">December 24, 2013</span></div><h1>Mutational effects on stability are largely conserved during protein evolution</h1><div class="text-gray-500 text-lg font-base my-3">Orr Ashenberg, Lizhi Ian Gong, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.pnas.org/doi/abs/10.1073/pnas.1314781111" target="_blank">10.1073/pnas.1314781111</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of virology</span><span class="pl-3">May 14, 2013</span></div><h1>Stability-mediated epistasis constrains the evolution of an influenza protein</h1><div class="text-gray-500 text-lg font-base my-3">Lizhi Ian Gong, Marc A Suchard, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/631" target="_blank">10.7554/eLife.00631.001</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of virology</span><span class="pl-3">December 1, 2013</span></div><h1>A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein</h1><div class="text-gray-500 text-lg font-base my-3">Kathryn A Hooper, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/jvi.01889-13" target="_blank">10.1128/jvi.01889-13</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA&#39;s receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Molecular biology and evolution</span><span class="pl-3">October 1, 2014</span></div><h1>An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/mbe/article/31/10/2753/1015257" target="_blank">10.1093/molbev/msu220</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not known a priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here, I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg E, Labonte JW, Gray JJ, Ostermeier M. 2014. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 31:1581–1592) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much better than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Molecular Biology and Evolution</span><span class="pl-3">August 1, 2014</span></div><h1>An experimentally determined evolutionary model dramatically improves phylogenetic fit</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/mbe/article/31/8/1956/2925795" target="_blank">10.1093/molbev/msu173</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS genetics</span><span class="pl-3">May 8, 2014</span></div><h1>Epistatically interacting substitutions are enriched during adaptive protein evolution</h1><div class="text-gray-500 text-lg font-base my-3">Lizhi Ian Gong, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328" target="_blank">10.1371/journal.pgen.1004328</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">July 8, 2014</span></div><h1>The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin</h1><div class="text-gray-500 text-lg font-base my-3">Bargavi Thyagarajan, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/3300" target="_blank">10.7554/eLife.03300</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein&#39;s structure and function, and can be used to create a model that describes hemagglutinin&#39;s evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza&#39;s antigenic evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">BMC bioinformatics</span><span class="pl-3">December 1, 2015</span></div><h1>Software for the analysis and visualization of deep mutational scanning data</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://link.springer.com/article/10.1186/s12859-015-0590-4" target="_blank">10.1186/s12859-015-0590-4</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.</p><p>I describe a software package, dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show that dms_tools yields more accurate inferences on simulated data than simply calculating ratios of counts pre- and post-selection. Using dms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Molecular biology and evolution</span><span class="pl-3">November 1, 2015</span></div><h1>Site-specific amino acid preferences are mostly conserved in two closely related protein homologs</h1><div class="text-gray-500 text-lg font-base my-3">Michael B Doud, Orr Ashenberg, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/mbe/article/32/11/2944/982113" target="_blank">10.1093/molbev/msv167</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Evolution drives changes in a protein’s sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of virology</span><span class="pl-3">April 1, 2015</span></div><h1>Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice</h1><div class="text-gray-500 text-lg font-base my-3">Kathryn A Hooper, James E Crowe Jr, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/jvi.00012-15" target="_blank">10.1128/jvi.00012-15</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids in viral release. However, in recent years, several groups have described point mutations that confer receptor-binding activity on NA, albeit in laboratory rather than natural settings. One of these mutations, D151G, appears to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. We inadvertently isolated the second of these mutations, G147R, in the NA of the lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus in the lab. G147R also occurs at low frequencies in the reported sequences of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA from each of these lineages and found that all of the proteins have acquired the ability to bind an unknown cellular receptor while retaining substantial sialidase activity. We then reconstructed a virus with the HA and NA of a reported G147R pdmH1N1 variant and found no attenuation of viral replication in cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had modestly enhanced resistance to neutralization by the Fab of an antibody against the receptor-binding pocket of HA, although it remained completely sensitive to the full-length IgG. Overall, our results suggest that circulating N1 viruses occasionally may acquire the G147R NA receptor-binding mutation without impairment of replicative capacity.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of virology</span><span class="pl-3">November 15, 2015</span></div><h1>Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages</h1><div class="text-gray-500 text-lg font-base my-3">Heather M Machkovech, Trevor Bedford, Marc A Suchard, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/jvi.01571-15" target="_blank">10.1128/jvi.01571-15</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">June 3, 2016</span></div><h1>Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin</h1><div class="text-gray-500 text-lg font-base my-3">Michael B Doud, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/8/6/155" target="_blank">10.3390/v8060155</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">December 13, 2016</span></div><h1>Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture</h1><div class="text-gray-500 text-lg font-base my-3">Hugh K Haddox, Adam S Dingens, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114" target="_blank">10.1371/journal.ppat.1006114</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selection in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture. We compare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured preferences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env. We show that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">March 15, 2016</span></div><h1>Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Kathryn A Hooper, Anja R Ollodart, Adam S Dingens, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/13974" target="_blank">10.7554/eLife.13974.001</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">March 27, 2017</span></div><h1>Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA</h1><div class="text-gray-500 text-lg font-base my-3">Orr Ashenberg, Jai Padmakumar, Michael B Doud, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288" target="_blank">10.1371/journal.ppat.1006288</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Biology direct</span><span class="pl-3">December 1, 2017</span></div><h1>Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://link.springer.com/article/10.1186/s13062-016-0172-z" target="_blank">10.1186/s13062-016-0172-z</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell host &amp; microbe</span><span class="pl-3">June 14, 2017</span></div><h1>Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Hugh K Haddox, Julie Overbaugh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf" target="_blank">10.1016/j.chom.2017.05.003</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Precisely defining how viral mutations affect HIV’s sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">March 13, 2017</span></div><h1>Complete mapping of viral escape from neutralizing antibodies</h1><div class="text-gray-500 text-lg font-base my-3">Michael B Doud, Scott E Hensley, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271" target="_blank">10.1371/journal.ppat.1006271</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PeerJ</span><span class="pl-3">July 31, 2017</span></div><h1>phydms: Software for phylogenetic analyses informed by deep mutational scanning</h1><div class="text-gray-500 text-lg font-base my-3">Sarah K Hilton, Michael B Doud, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://peerj.com/articles/3657/" target="_blank">10.7717/peerj.3657</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">June 27, 2017</span></div><h1>Parallel evolution of influenza across multiple spatiotemporal scales</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Terry Stevens-Ayers, Angela P Campbell, Janet A Englund, Steven A Pergam, Michael Boeckh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/26875" target="_blank">10.7554/eLife.26875.001</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">July 5, 2018</span></div><h1>Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Priyamvada Acharya, Hugh K Haddox, Reda Rawi, Kai Xu, Gwo-Yu Chuang, Hui Wei, Baoshan Zhang, John R Mascola, Bridget Carragher, Clinton S Potter, Julie Overbaugh, Peter D Kwong, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159" target="_blank">10.1371/journal.ppat.1007159</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env’s fusion peptide.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature communications</span><span class="pl-3">April 11, 2018</span></div><h1>How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin</h1><div class="text-gray-500 text-lg font-base my-3">Michael B Doud*, Juhye M Lee*, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41467-018-03665-3" target="_blank">10.1038/s41467-018-03665-3</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">March 28, 2018</span></div><h1>Mapping mutational effects along the evolutionary landscape of HIV envelope</h1><div class="text-gray-500 text-lg font-base my-3">Hugh K Haddox*, Adam S Dingens*, Sarah K Hilton, Julie Overbaugh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/34420" target="_blank">10.7554/eLife.34420</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at &gt; 100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus evolution</span><span class="pl-3">July 1, 2018</span></div><h1>Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence</h1><div class="text-gray-500 text-lg font-base my-3">Sarah K Hilton, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/4/2/vey033/5163287" target="_blank">10.1093/ve/vey033</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PNAS</span><span class="pl-3">August 28, 2018</span></div><h1>Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants</h1><div class="text-gray-500 text-lg font-base my-3">Juhye M Lee, John Huddleston, Michael B Doud, Kathryn A Hooper, Nicholas C Wu, Trevor Bedford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.pnas.org/doi/abs/10.1073/pnas.1806133115" target="_blank">10.1073/pnas.1806133115</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA’s functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature—but only when the measurements are made on a viral strain similar to the ones being studied in nature.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">February 16, 2018</span></div><h1>Extreme heterogeneity of influenza virus infection in single cells</h1><div class="text-gray-500 text-lg font-base my-3">Alistair B Russell, Cole Trapnell, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/32303" target="_blank">10.7554/eLife.32303</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Trends in Microbiology</span><span class="pl-3">September 1, 2018</span></div><h1>Within-host evolution of human influenza virus</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Louise H Moncla, Trevor Bedford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X" target="_blank">10.1016/j.tim.2018.02.007</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus&#39;s global evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">MSphere</span><span class="pl-3">February 28, 2018</span></div><h1>Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Alexander L Greninger, Ailyn Pérez-Osorio, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17" target="_blank">10.1128/mspheredirect.00552-17</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">JOSS</span><span class="pl-3">January 23, 2019</span></div><h1>alignparse: A Python package for parsing complex features from high-throughput long-read sequencing</h1><div class="text-gray-500 text-lg font-base my-3">Katharine HD Crawford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://doi.org/10.21105%2Fjoss.01915" target="_blank">10.21105/joss.01915</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Hebert et al., 2018; Rhoads &amp; Au, 2015). Good programs exist for aligning these reads for genome assembly (Chaisson &amp; Tesler, 2012; Li, 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al, 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al., 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">May 15, 2019</span></div><h1>Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Dana Arenz, Julie Overbaugh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/11/5/439" target="_blank">10.3390/v11050439</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by studying viral evolution within treated patients or during viral growth in the presence of a drug in cell culture. Such approaches have previously mapped resistance to enfuvirtide, the only clinically approved HIV-1 fusion inhibitor, to enfuvirtide’s binding site in the N-terminal heptad repeat (NHR) of the Envelope (Env) transmembrane domain as well as a limited number of allosteric sites. Here, we sought to better delineate the genotypic determinants of resistance throughout Env. We used deep mutational scanning to quantify the effect of all single-amino-acid mutations to the subtype A BG505 Env on resistance to enfuvirtide. We identified both previously characterized and numerous novel resistance mutations in the NHR. Additional resistance mutations clustered in other regions of Env conformational intermediates, suggesting they may act during different fusion steps by altering fusion kinetics and/or exposure of the enfuvirtide binding site. This complete map of resistance sheds light on the diverse mechanisms of enfuvirtide resistance and highlights the utility of using deep mutational scanning to comprehensively map potential drug resistance mutations.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Immunity</span><span class="pl-3">February 19, 2019</span></div><h1>An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub" target="_blank">10.1016/j.immuni.2018.12.017</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’s independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">August 27, 2019</span></div><h1>Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin</h1><div class="text-gray-500 text-lg font-base my-3">Juhye M Lee, Rachel Eguia, Seth J Zost, Saket Choudhary, Patrick C Wilson, Trevor Bedford, Terry Stevens-Ayers, Michael Boeckh, Aeron C Hurt, Seema S Lakdawala, Scott E Hensley, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/49324" target="_blank">10.7554/eLife.49324</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">January 23, 2019</span></div><h1>Comprehensive profiling of translation initiation in influenza virus infected cells</h1><div class="text-gray-500 text-lg font-base my-3">Heather M Machkovech, Jesse D Bloom, Arvind R Subramaniam</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518" target="_blank">10.1371/journal.ppat.1007518</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Translation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactimidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. We do not detect globally higher levels of alternate translation initiation on host transcripts upon influenza infection or during the anti-viral response, but the subset of host transcripts induced by the anti-viral response is enriched for alternate initiation sites. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of virology</span><span class="pl-3">July 15, 2019</span></div><h1>Single-cell virus sequencing of influenza infections that trigger innate immunity</h1><div class="text-gray-500 text-lg font-base my-3">Alistair B Russell, Elizaveta Elshina, Jacob R Kowalsky, Aartjan JW Te Velthuis, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/jvi.00500-19" target="_blank">10.1128/jvi.00500-19</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally “pure” stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus’s interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to—but does not completely explain—the heterogeneity in viral gene expression and immune activation in single infected cells.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">April 30, 2019</span></div><h1>Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans</h1><div class="text-gray-500 text-lg font-base my-3">YQ Shirleen Soh, Louise H Moncla, Rachel Eguia, Trevor Bedford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://doi.org/10.7554/eLife.45079" target="_blank">10.7554/eLife.45079</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2’s surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature genetics</span><span class="pl-3">September 1, 2019</span></div><h1>Reconciling disparate estimates of viral genetic diversity during human influenza infections</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41588-019-0349-3" target="_blank">10.1038/s41588-019-0349-3</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>To the Editor — A key question in the study of influenza virus evolution is how rapidly viral genetic variation arises within infected humans1,2. Recently, several studies have measured influenza’s within-host genetic diversity in large cohorts of infected humans through high-throughput deep sequencing3,4,5,6 (Supplementary Table 1). These studies disagree in their estimates of influenza’s within-host genetic diversity. In a Nature Genetics letter titled ‘Quantifying influenza virus diversity and transmission in humans’, analyzing a household cohort in Hong Kong, Poon et al.4 have estimated that within-host genetic diversity is high, and 200–250 viral genomes are transmitted between individuals. However, several recent studies conducted in Wisconsin3, Michigan6, and Washington7 that used similar methodologies have estimated lower levels of viral genetic diversity. In particular, the Michigan study has estimated a narrow transmission bottleneck of just one or two viral genomes6. We sought to examine whether technical differences in the underlying deep-sequencing datasets or the methods used to analyze them might explain the disparate estimates of within-host viral genetic diversity. We identified an anomaly in the Hong Kong data that provides a technical explanation for these discrepancies: read pairs from this study are often split between different biological samples, thus indicating that some reads are incorrectly assigned.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">May 6, 2020</span></div><h1>Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays</h1><div class="text-gray-500 text-lg font-base my-3">Katharine HD Crawford, Rachel Eguia, Adam S Dingens, Andrea N Loes, Keara D Malone, Caitlin R Wolf, Helen Y Chu, M Alejandra Tortorici, David Veesler, Michael Murphy, Deleah Pettie, Neil P King, Alejandro B Balazs, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/12/5/513" target="_blank">10.3390/v12050513</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) particles, but the reagents and protocols are not widely available. Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2. We also made all the key experimental reagents available in the BEI Resources repository of ATCC and the NIH. Furthermore, we demonstrated how these pseudotyped lentiviral particles could be used to measure the neutralizing activity of human sera or plasma against SARS-CoV-2 in convenient luciferase-based assays, thereby providing a valuable complement to ELISA-based methods that measure antibody binding rather than neutralization.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature communications</span><span class="pl-3">September 1, 2020</span></div><h1>Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Katharine HD Crawford, Amanda Adler, Sarah L Steele, Kirsten Lacombe, Rachel Eguia, Fatima Amanat, Alexandra C Walls, Caitlin R Wolf, Michael Murphy, Deleah Pettie, Lauren Carter, Xuan Qin, Neil P King, David Veesler, Florian Krammer, Jane A Dickerson, Helen Y Chu, Janet A Englund, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41467-020-18178-1" target="_blank">10.1038/s41467-020-18178-1</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution &gt; 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS computational biology</span><span class="pl-3">May 4, 2020</span></div><h1>When two are better than one: Modeling the mechanisms of antibody mixtures</h1><div class="text-gray-500 text-lg font-base my-3">Tal Einav, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830" target="_blank">10.1371/journal.pcbi.1007830</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>It is difficult to predict how antibodies will behave when mixed together, even after each has been independently characterized. Here, we present a statistical mechanical model for the activity of antibody mixtures that accounts for whether pairs of antibodies bind to distinct or overlapping epitopes. This model requires measuring n individual antibodies and their pairwise interactions to predict the 2n potential combinations. We apply this model to epidermal growth factor receptor (EGFR) antibodies and find that the activity of antibody mixtures can be predicted without positing synergy at the molecular level. In addition, we demonstrate how the model can be used in reverse, where straightforward experiments measuring the activity of antibody mixtures can be used to infer the molecular interactions between antibodies. Lastly, we generalize this model to analyze engineered multidomain antibodies, where components of different antibodies are tethered together to form novel amalgams, and characterize how well it predicts recently designed influenza antibodies.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">May 30, 2020</span></div><h1>Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding</h1><div class="text-gray-500 text-lg font-base my-3">Lauren E Gentles, Hongquan Wan, Maryna C Eichelberger, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/12/6/597" target="_blank">10.3390/v12060597</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. However, antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, a virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable the selection of viral escape mutants.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">JOSS</span><span class="pl-3">August 17, 2020</span></div><h1>dms-view: Interactive visualization tool for deep mutational scanning data</h1><div class="text-gray-500 text-lg font-base my-3">Sarah K Hilton*, John Huddleston*, Allison Black, Khrystyna North, Adam S Dingens, Trevor Bedford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://joss.theoj.org/papers/10.21105/joss.02353" target="_blank">10.21105/joss.02353</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Here we describe dms-view (<a href="https://dms-view.github.io/" target="_blank" rel="noreferrer">https://dms-view.github.io/</a>), a flexible, web-based, interactive visualization tool for DMS data.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">September 5, 2020</span></div><h1>Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice</h1><div class="text-gray-500 text-lg font-base my-3">Andrea N Loes, Lauren E Gentles, Allison J Greaney, Katharine HD Crawford, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/12/9/987" target="_blank">10.3390/v12090987</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">February 21, 2020</span></div><h1>Identification of HIV-1 envelope mutations that enhance entry using macaque CD4 and CCR5</h1><div class="text-gray-500 text-lg font-base my-3">Jeremy I Roop, Noah A Cassidy, Adam S Dingens, Jesse D Bloom, Julie Overbaugh</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/12/2/241" target="_blank">10.3390/v12020241</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env’s gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque receptors. We identified many uncharacterized amino acid mutations in the N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of gp41 that increased entry into cells bearing macaque receptors up to 9-fold. Many of these mutations also modestly increased infection of cells bearing human CD4 and CCR5 (up to 1.5-fold). NHR/CHR mutations identified by deep mutational scanning that enhanced entry also increased sensitivity to neutralizing antibodies targeting the MPER epitope, and to inactivation by cold-incubation, suggesting that they promote sampling of an intermediate trimer conformation between closed and receptor bound states. Identification of this set of mutations can inform future macaque model studies, and also further our understanding of the relationship between Env structure and function.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell</span><span class="pl-3">September 3, 2020</span></div><h1>Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr*, Allison J Greaney*, Sarah K Hilton, Daniel Ellis, Katharine HD Crawford, Adam S Dingens, Mary Jane Navarro, John E Bowen, Alejandra M Tortorici, Alexandra C Walls, Neil P King, David Veesler, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub" target="_blank">10.1016/j.cell.2020.08.012</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus evolution</span><span class="pl-3">January 1, 2020</span></div><h1>Linking influenza virus evolution within and between human hosts</h1><div class="text-gray-500 text-lg font-base my-3">Katherine S Xue, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/6/1/veaa010/5739536" target="_blank">10.1093/ve/veaa010</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">mBio</span><span class="pl-3">December 1, 2021</span></div><h1>Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/mbe/article/38/12/5211/6353034" target="_blank">10.1093/molbev/msab246</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH’s Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2’s bat coronavirus relatives.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">The Journal of infectious diseases</span><span class="pl-3">January 15, 2021</span></div><h1>Dynamics of neutralizing antibody titers in the months after severe acute respiratory syndrome coronavirus 2 infection</h1><div class="text-gray-500 text-lg font-base my-3">Katharine HD Crawford, Adam S Dingens, Rachel Eguia, Caitlin R Wolf, Naomi Wilcox, Jennifer K Logue, Kiel Shuey, Amanda M Casto, Brooke Fiala, Samuel Wrenn, Deleah Pettie, Neil P King, Alexander L Greninger, Helen Y Chu, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/jid/article/223/2/197/5916372" target="_blank">10.1093/infdis/jiaa618</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">January 13, 2021</span></div><h1>High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination</h1><div class="text-gray-500 text-lg font-base my-3">Adam S Dingens, Payal Pratap, Keara Malone, Sarah K Hilton, Thomas Ketas, Christopher A Cottrell, Julie Overbaugh, John P Moore, PJ Klasse, Andrew B Ward, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/64281" target="_blank">10.7554/eLife.64281</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. We used mutational antigenic profiling to determine how all mutations in Env affected viral neutralization and electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize serum Fabs bound to Env trimers. The dominant neutralizing specificities were generally only a subset of the more diverse binding specificities. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Furthermore, we refined residue-level epitope specificity directly from sera, revealing subtle differences across sera. Together, mutational antigenic profiling and EMPEM yield a holistic view of the binding and neutralizing specificity of polyclonal sera.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">April 8, 2021</span></div><h1>A human coronavirus evolves antigenically to escape antibody immunity</h1><div class="text-gray-500 text-lg font-base my-3">Rachel T Eguia, Katharine HD Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L Greninger, Janet A Englund, Michael J Boeckh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009453" target="_blank">10.1371/journal.ppat.1009453</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers &gt;1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature Communications</span><span class="pl-3">July 7, 2021</span></div><h1>Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Tyler N Starr, Christopher O Barnes, Yiska Weisblum, Fabian Schmidt, Marina Caskey, Christian Gaebler, Alice Cho, Marianna Agudelo, Shlomo Finkin, Zijun Wang, Daniel Poston, Frauke Muecksch, Theodora Hatziioannou, Paul D Bieniasz, Davide F Robbiani, Michel C Nussenzweig, Pamela J Bjorkman, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41467-021-24435-8" target="_blank">10.1038/s41467-021-24435-8</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Science translational medicine</span><span class="pl-3">June 30, 2021</span></div><h1>Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Andrea N Loes, Lauren E Gentles, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.science.org/doi/full/10.1126/scitranslmed.abi9915" target="_blank">10.1126/scitranslmed.abi9915</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell host &amp; microbe</span><span class="pl-3">March 10, 2021</span></div><h1>Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Andrea N Loes, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf" target="_blank">10.1016/j.chom.2021.02.003</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced &gt;10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell host &amp; microbe</span><span class="pl-3">January 13, 2021</span></div><h1>Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney*, Tyler N Starr*, Pavlo Gilchuk, Seth J Zost, Elad Binshtein, Andrea N Loes, Sarah K Hilton, John Huddleston, Rachel Eguia, Katharine HD Crawford, Adam S Dingens, Rachel S Nargi, Rachel E Sutton, Naveenchandra Suryadevara, Paul W Rothlauf, Zhuoming Liu, Sean PJ Whelan, Robert H Carnahan, James E Crowe, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf" target="_blank">10.1016/j.chom.2020.11.007</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell Reports Medicine</span><span class="pl-3">April 20, 2021</span></div><h1>Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Frances C Welsh, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.sciencedirect.com/science/article/pii/S2666379121000732?via%3Dihub" target="_blank">10.1016/j.xcrm.2021.100257</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Munoz-Alia and colleagues demonstrate that neutralizing antibody immunity to measles resists viral evolutionary escape because it targets numerous distinct viral epitopes. Their work contributes to our understanding of what determines whether a virus can evolve to evade immunity.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">June 22, 2021</span></div><h1>Comprehensive profiling of mutations to influenza virus PB2 that confer resistance to the cap-binding inhibitor pimodivir</h1><div class="text-gray-500 text-lg font-base my-3">Shirleen YQ Soh, Keara D Malone, Rachel T Eguia, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/13/7/1196" target="_blank">10.3390/v13071196</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell Reports Medicine</span><span class="pl-3">April 20, 2021</span></div><h1>Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr, Allison J Greaney, Adam S Dingens, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf" target="_blank">10.1016/j.xcrm.2021.100255</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Science</span><span class="pl-3">February 19, 2021</span></div><h1>Prospective mapping of viral mutations that escape antibodies used to treat COVID-19</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr*, Allison J Greaney*, Amin Addetia, William W Hannon, Manish C Choudhary, Adam S Dingens, Jonathan Z Li, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.science.org/doi/full/10.1126/science.abf9302" target="_blank">10.1126/science.abf9302</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature</span><span class="pl-3">September 2, 2021</span></div><h1>SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr, Nadine Czudnochowski, Zhuoming Liu, Fabrizia Zatta, Young-Jun Park, Amin Addetia, Dora Pinto, Martina Beltramello, Patrick Hernandez, Allison J Greaney, Roberta Marzi, William G Glass, Ivy Zhang, Adam S Dingens, John E Bowen, M Alejandra Tortorici, Alexandra C Walls, Jason A Wojcechowskyj, Anna De Marco, Laura E Rosen, Jiayi Zhou, Martin Montiel-Ruiz, Hannah Kaiser, Josh R Dillen, Heather Tucker, Jessica Bassi, Chiara Silacci-Fregni, Michael P Housley, Julia di Iulio, Gloria Lombardo, Maria Agostini, Nicole Sprugasci, Katja Culap, Stefano Jaconi, Marcel Meury, Exequiel Dellota Jr, Rana Abdelnabi, Shi-Yan Caroline Foo, Elisabetta Cameroni, Spencer Stumpf, Tristan I Croll, Jay C Nix, Colin Havenar-Daughton, Luca Piccoli, Fabio Benigni, Johan Neyts, Amalio Telenti, Florian A Lempp, Matteo S Pizzuto, John D Chodera, Christy M Hebner, Herbert W Virgin, Sean PJ Whelan, David Veesler, Davide Corti, Jesse D Bloom, Gyorgy Snell</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41586-021-03807-6" target="_blank">10.1038/s41586-021-03807-6</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse sarbecoviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Viruses</span><span class="pl-3">September 16, 2022</span></div><h1>Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2</h1><div class="text-gray-500 text-lg font-base my-3">Ariana Ghez Farrell*, Bernadeta Dadonaite*, Allison J Greaney, Rachel Eguia, Andrea N Loes, Nicholas M Franko, Jennifer Logue, Juan Manuel Carreño, Anass Abbad, Helen Y Chu, Kenneth A Matreyek, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.mdpi.com/1999-4915/14/9/2061" target="_blank">10.3390/v14092061</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">medRxiv</span><span class="pl-3">January 25, 2022</span></div><h1>Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time</h1><div class="text-gray-500 text-lg font-base my-3">Lauren E Gentles, Leanne Kehoe, Katharine HD Crawford, Kirsten Lacombe, Jane Dickerson, Caitlin Wolf, Joanna Yuan, Susanna Schuler, John T Watson, Sankan Nyanseor, Melissa Briggs-Hagen, Sharon Saydah, Claire M Midgley, Kimberly Pringle, Helen Chu, Jesse D Bloom, Janet A Englund</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1" target="_blank">10.1101/2022.01.14.22269235</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS Pathogens</span><span class="pl-3">June 29, 2022</span></div><h1>The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Rachel T Eguia, Tyler N Starr, Khadija Khan, Nicholas Franko, Jennifer K Logue, Sandra M Lord, Cate Speake, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592" target="_blank">10.1371/journal.ppat.1010592</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">February 8, 2022</span></div><h1>A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Tyler N Starr, Rachel T Eguia, Andrea N Loes, Khadija Khan, Farina Karim, Sandile Cele, John E Bowen, Jennifer K Logue, Davide Corti, David Veesler, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248" target="_blank">10.1371/journal.ppat.1010248</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">January 1, 2022</span></div><h1>An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain</h1><div class="text-gray-500 text-lg font-base my-3">Allison J Greaney, Tyler N Starr, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/8/1/veac021/6549895" target="_blank">10.1093/ve/veac021</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at <a href="https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/" target="_blank" rel="noreferrer">https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/</a> (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">July 1, 2022</span></div><h1>Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat</h1><div class="text-gray-500 text-lg font-base my-3">William W Hannon, Pavitra Roychoudhury, Hong Xie, Lasata Shrestha, Amin Addetia, Keith R Jerome, Alexander L Greninger, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/8/2/veac052/6609212" target="_blank">10.1093/ve/veac052</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here, we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting that viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature</span><span class="pl-3">March 31, 2022</span></div><h1>ACE2 binding is an ancestral and evolvable trait of sarbecoviruses</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr, Samantha K Zepeda, Alexandra C Walls, Allison J Greaney, Sergey Alkhovsky, David Veesler, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41586-022-04464-z" target="_blank">10.1038/s41586-022-04464-z</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Two different sarbecoviruses have caused major human outbreaks in the past two decades. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">PLoS pathogens</span><span class="pl-3">November 18, 2022</span></div><h1>Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr*, Allison J Greaney*, Cameron M Stewart, Alexandra C Walls, William W Hannon, David Veesler, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951" target="_blank">10.1371/journal.ppat.1010951</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Science</span><span class="pl-3">July 22, 2022</span></div><h1>Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution</h1><div class="text-gray-500 text-lg font-base my-3">Tyler N Starr*, Allison J Greaney*, William W Hannon, Andrea N Loes, Kevin Hauser, Josh R Dillen, Elena Ferri, Ariana Ghez Farrell, Bernadeta Dadonaite, Matthew McCallum, Kenneth A Matreyek, Davide Corti, David Veesler, Gyorgy Snell, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.science.org/doi/full/10.1126/science.abo7896" target="_blank">10.1126/science.abo7896</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn501→Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">July 1, 2022</span></div><h1>A biophysical model of viral escape from polyclonal antibodies</h1><div class="text-gray-500 text-lg font-base my-3">Timothy C Yu, Zorian T Thornton, William W Hannon, William S DeWitt, Caelan E Radford, Frederick A Matsen IV, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank">10.1093/ve/veac110</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at <a href="https://jbloomlab.github.io/polyclonal" target="_blank" rel="noreferrer">https://jbloomlab.github.io/polyclonal</a>.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">eLife</span><span class="pl-3">September 7, 2023</span></div><h1>Influenza virus transcription and progeny production are poorly correlated in single cells</h1><div class="text-gray-500 text-lg font-base my-3">David J Bacsik, Bernadeta Dadonaite, Andrew Butler, Allison J Greaney, Nicholas S Heaton, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://elifesciences.org/articles/86852" target="_blank">10.7554/eLife.86852.2</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell’s contribution to the progeny population.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">July 1, 2023</span></div><h1>Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/9/2/vead050/7249794" target="_blank">10.1093/ve/vead050</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The role of the Huanan Seafood Market in the early severe acute respiratory syndrome virus 2 (SARS-CoV-2) outbreak remains unclear. Recently, the Chinese Centers for Disease Control (CDC) released data from deep sequencing of environmental samples collected from the market after it was closed on 1 January 2020. Prior to this release, Crits-Christoph et al. analyzed data from a subset of the samples. Both that study and the Chinese CDC study concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. However, the SARS-CoV-2 content of the environmental samples is generally very low: only 21 of 176 samples contain more than ten SARS-CoV-2 reads, despite most samples being sequenced to depths exceeding 10**8 total reads. None of the samples with double-digit numbers of SARS-CoV-2 reads have a substantial fraction of their mitochondrial material from any non-human susceptible species. Only one of the fourteen samples with at least a fifth of the chordate mitochondrial material from raccoon dogs contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Molecular Biology and Evolution</span><span class="pl-3">April 11, 2023</span></div><h1>Evolution of the SARS-CoV-2 mutational spectrum</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/mbe/article/40/4/msad085/7113660" target="_blank">10.1093/molbev/msad085</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">September 18, 2023</span></div><h1>Fitness effects of mutations to SARS-CoV-2 proteins</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom, Richard A Neher</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank">10.1093/ve/veae026</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (<a href="https://jbloomlab.github.io/SARS2-mut-fitness/" target="_blank" rel="noreferrer">https://jbloomlab.github.io/SARS2-mut-fitness/</a>). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell</span><span class="pl-3">March 16, 2023</span></div><h1>A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike</h1><div class="text-gray-500 text-lg font-base my-3">Bernadeta Dadonaite*, Katharine HD Crawford*, Caelan E Radford*, Ariana G Farrell, C Yu Timothy, William W Hannon, Panpan Zhou, Raiees Andrabi, Dennis R Burton, Lihong Liu, David D Ho, Helen Y Chu, Richard A Neher, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf" target="_blank">10.1016/j.cell.2023.02.001</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of Virology</span><span class="pl-3">November 30, 2023</span></div><h1>The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies</h1><div class="text-gray-500 text-lg font-base my-3">Caroline Kikawa, Catiana H Cartwright-Acar, Jackson B Stuart, Maya Contreras, Lisa M Levoir, Matthew J Evans, Jesse D Bloom, Leslie Goo</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://journals.asm.org/doi/full/10.1128/jvi.01414-23" target="_blank">10.1128/jvi.01414-23</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell Host &amp; Microbe</span><span class="pl-3">July 12, 2023</span></div><h1>Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning</h1><div class="text-gray-500 text-lg font-base my-3">Caelan E Radford, Philipp Schommers, Lutz Gieselmann, Katharine HD Crawford, Bernadeta Dadonaite, Timothy C Yu, Adam S Dingens, Julie Overbaugh, Florian Klein, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf" target="_blank">10.1016/j.chom.2023.05.025</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Understanding the specificities of human serum antibodies that broadly neutralize HIV can inform prevention and treatment strategies. Here, we describe a deep mutational scanning system that can measure the effects of combinations of mutations to HIV envelope (Env) on neutralization by antibodies and polyclonal serum. We first show that this system can accurately map how all functionally tolerated mutations to Env affect neutralization by monoclonal antibodies. We then comprehensively map Env mutations that affect neutralization by a set of human polyclonal sera that neutralize diverse strains of HIV and target the site engaging the host receptor CD4. The neutralizing activities of these sera target different epitopes, with most sera having specificities reminiscent of individual characterized monoclonal antibodies, but one serum targeting two epitopes within the CD4-binding site. Mapping the specificity of the neutralizing activity in polyclonal human serum will aid in assessing anti-HIV immune responses to inform prevention strategies.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Virus Evolution</span><span class="pl-3">January 1, 2024</span></div><h1>Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market</h1><div class="text-gray-500 text-lg font-base my-3">Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://academic.oup.com/ve/article/10/1/vead089/7504441" target="_blank">10.1093/ve/vead089</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>In March 2023, the Chinese CDC publicly released raw metagenomic sequencing data for environmental samples collected in early 2020 from the Huanan Seafood Market. Prior to that data release, some scientists had suggested that these samples could be informative for establishing if animals such as raccoon dogs had been infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2). However, no one had analyzed how much SARS-CoV-2 was actually present in the metagenomic sequencing data. After the raw data became available, I fully analyzed the abundance of both viral and animal genetic material in the samples. That analysis, which was published in Virus Evolution, found that the SARS-CoV-2 content of most samples was very low and that the abundance of SARS-CoV-2 was most strongly associated with animals such as largemouth bass that are not plausible candidates for having been infected. Based on these results, I concluded that the metagenomic content of the samples was not informative for determining if any non-human animals in the market had been infected with SARS-CoV-2. One of the authors of an earlier study of these samples, Florence Débarre, recently submitted a response to my paper. Here, I reply in turn to explain why it is important to quantify the abundance of viral material before drawing conclusions from metagenomic sequencing. I also report new analyses of other animal coronaviruses in the samples and show that material from some other animal coronaviruses is much more abundant than SARS-CoV-2 in samples collected on the date when most wildlife stall sampling was performed. I further show that material from some of these animal coronaviruses is associated with the animals they probably infect but that no such association exists for SARS-CoV-2. Overall, these new analyses further emphasize the importance of quantifying the actual amount of viral material in metagenomic samples and underscore why the environmental samples from the Huanan Seafood Market are not informative for determining if any non-human animals were infected with SARS-CoV-2.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Immunity</span><span class="pl-3">July 15, 2024</span></div><h1>Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex</h1><div class="text-gray-500 text-lg font-base my-3">Caleb R Carr*, Katharine HD Crawford*, Michael Murphy, Jared G Galloway, Hugh K Haddox, Frederick A Matsen, Kristian G Andersen, Neil P King, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4" target="_blank">10.1016/j.immuni.2024.06.013</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/LASV_Josiah_GP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/LASV_Josiah_GP_DMS/</a></p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Nature</span><span class="pl-3">July 3, 2024</span></div><h1>Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades</h1><div class="text-gray-500 text-lg font-base my-3">Bernadeta Dadonaite, Jack Brown, Teagan E McMahon, Ariana G Farrell, Marlin D Figgins, Daniel Asarnow, Cameron Stewart, Jimin Lee, Jenni Logue, Trevor Bedford, Ben Murrell, Helen Y Chu, David Veesler, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank">10.1038/s41586-024-07636-1</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>SARS-CoV-2 variants acquire mutations in spike that promote immune evasion and impact other properties that contribute to viral fitness such as ACE2 receptor binding and cell entry. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning to measure how &gt;9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry, or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully impacted ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5 spike affect neutralization by serum from individuals who recently had SARS-CoV-2 infections. The strongest serum escape mutations are in the RBD at sites 357, 420, 440, 456, and 473—however, the antigenic impacts of these mutations vary across individuals. We also identify strong escape mutations outside the RBD; however many of them decrease ACE2 binding, suggesting they act by modulating RBD conformation. Notably, the growth rates of human SARS-CoV-2 clades can be explained in substantial part by the measured effects of mutations on spike phenotypes, suggesting our data could enable better prediction of viral evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">bioRxiv</span><span class="pl-3">May 23, 2024</span></div><h1>Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance</h1><div class="text-gray-500 text-lg font-base my-3">Bernadeta Dadonaite, Jenny J Ahn, Jordan T Ort, Jin Yu, Colleen Furey, Annie Dosey, William W Hannon, Amy Vincent Baker, Richard J Webby, Neil P King, Yan Liu, Scott E Hensley, Thomas P Peacock, Louise H Moncla, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank">10.1101/2024.05.23.595634</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple non-human mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the &gt;10,000 different possible amino-acid mutations to HA. Here we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids, and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine strains. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of Open Source Software</span><span class="pl-3">July 17, 2024</span></div><h1>dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets</h1><div class="text-gray-500 text-lg font-base my-3">William W Hannon, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://joss.theoj.org/papers/10.21105/joss.06129" target="_blank">10.21105/joss.06129</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).</p><p>The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool, dms-viz. With dms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. See <a href="https://dms-viz.github.io/" target="_blank" rel="noreferrer">https://dms-viz.github.io/</a> to use dms-viz.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">bioRxiv</span><span class="pl-3">April 17, 2024</span></div><h1>Functional and antigenic landscape of the Nipah virus receptor binding protein</h1><div class="text-gray-500 text-lg font-base my-3">Brendan B Larsen, Teagan McMahon, Jack T Brown, Zhaoqian Wang, Caelan E Radford, James E Crowe, David Veesler, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract" target="_blank">10.1101/2024.04.17.589977</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies, and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.</p><h2 id="interactive-visualizations" tabindex="-1">Interactive visualizations <a class="header-anchor" href="#interactive-visualizations" aria-label="Permalink to &quot;Interactive visualizations&quot;">​</a></h2><p>The results described in this paper can be interactively visualized at <a href="https://dms-vep.org/Nipah_Malaysia_RBP_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Nipah_Malaysia_RBP_DMS/</a></p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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-    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">bioRxiv</span><span class="pl-3">March 8, 2024</span></div><h1>High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</h1><div class="text-gray-500 text-lg font-base my-3">Andrea N Loes, Rosario Araceli L Tarabi, John Huddleston, Lisa Touyon, Sook San Wong, Samuel MS Cheng, Nancy HL Leung, William W Hannon, Trevor Bedford, Sarah Cobey, Benjamin J Cowling, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract" target="_blank">10.1101/2024.03.08.584176</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: <a href="https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1" target="_blank" rel="noreferrer">https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1</a>) and a computational pipeline (<a href="https://github.com/jbloomlab/seqneut-pipeline" target="_blank" rel="noreferrer">https://github.com/jbloomlab/seqneut-pipeline</a>) for the sequencing-based neutralization assays to facilitate the use of this method by others.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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+    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Journal of Virology</span><span class="pl-3">September 24, 2024</span></div><h1>High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</h1><div class="text-gray-500 text-lg font-base my-3">Andrea N Loes, Rosario Araceli L Tarabi, John Huddleston, Lisa Touyon, Sook San Wong, Samuel MS Cheng, Nancy HL Leung, William W Hannon, Trevor Bedford, Sarah Cobey, Benjamin J Cowling, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://doi.org/10.1128/jvi.00689-24" target="_blank">10.1128/jvi.00689-24</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year—although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: <a href="https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1" target="_blank" rel="noreferrer">https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1</a>) and a computational pipeline (<a href="https://github.com/jbloomlab/seqneut-pipeline" target="_blank" rel="noreferrer">https://github.com/jbloomlab/seqneut-pipeline</a>) for the sequencing-based neutralization assays to facilitate the use of this method by others.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><div class="text-gray-500 text-lg font-medium flex divide-x divide-gray-300 mb-3"><span class="italic pr-3">Cell Host &amp; Microbe</span><span class="pl-3">July 19, 2024</span></div><h1>Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin</h1><div class="text-gray-500 text-lg font-base my-3">Frances C Welsh, Rachel T Eguia, Juhye M Lee, Hugh K Haddox, Jared Galloway, Nguyen Van Vinh Chau, Andrea N Loes, John Huddleston, Timothy C Yu, Mai Quynh Le, Nguyen TD Nhat, Nguyen Thi Le Thanh, Alexander L Greninger, Helen Y Chu, Janet A Englund, Trevor Bedford, Frederick A Matsen IV, Maciej F Boni, Jesse D Bloom</div><span class="text-gray-500 text-base font-medium"> doi:<a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6" target="_blank">10.1016/j.chom.2024.06.015</a></span><!--[--><div style="position:relative;"><div><h2 id="abstract" tabindex="-1">Abstract <a class="header-anchor" href="#abstract" aria-label="Permalink to &quot;Abstract&quot;">​</a></h2><p>Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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-    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="divide-y divide-gray-200"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14"> Papers </h1><p class="text-xl leading-8 text-gray-800"> Papers from the Bloom Lab team. See also <a href="https://scholar.google.com/citations?user=S12x_eQAAAAJ&amp;hl" target="_blank">Google Scholar</a> for a complete list of publications. </p><div class="p-multiselect p-component p-inputwrapper w-full md:w-80" style="" data-pc-name="multiselect" data-pc-section="root"><div class="p-hidden-accessible" data-pc-section="hiddeninputcontainer" data-p-hidden-accessible="true"><input type="text" readonly placeholder="Filter by Keywords" tabindex="0" role="combobox" aria-haspopup="listbox" aria-expanded="false" aria-controls="undefined_list" data-pc-section="hiddeninput"></div><div class="p-multiselect-label-container" data-pc-section="labelcontainer"><div class="p-multiselect-label p-placeholder" data-pc-section="label"><!--[--><!--[-->Filter by Keywords<!--]--><!--]--></div></div><div class="p-multiselect-dropdown" data-pc-section="dropdown"><!--[--><svg width="14" height="14" viewBox="0 0 14 14" fill="none" xmlns="http://www.w3.org/2000/svg" class="p-icon p-multiselect-dropdown-icon" aria-hidden="true" data-pc-section="dropdownicon"><path d="M7.01744 10.398C6.91269 10.3985 6.8089 10.378 6.71215 10.3379C6.61541 10.2977 6.52766 10.2386 6.45405 10.1641L1.13907 4.84913C1.03306 4.69404 0.985221 4.5065 1.00399 4.31958C1.02276 4.13266 1.10693 3.95838 1.24166 3.82747C1.37639 3.69655 1.55301 3.61742 1.74039 3.60402C1.92777 3.59062 2.11386 3.64382 2.26584 3.75424L7.01744 8.47394L11.769 3.75424C11.9189 3.65709 12.097 3.61306 12.2748 3.62921C12.4527 3.64535 12.6199 3.72073 12.7498 3.84328C12.8797 3.96582 12.9647 4.12842 12.9912 4.30502C13.0177 4.48162 12.9841 4.662 12.8958 4.81724L7.58083 10.1322C7.50996 10.2125 7.42344 10.2775 7.32656 10.3232C7.22968 10.3689 7.12449 10.3944 7.01744 10.398Z" fill="currentColor"></path></svg><!--]--></div><!----></div></div><div class="selected-publications mb-8"><h2 class="text-3xl leading-8 font-bold text-gray-800 tracking-tight mt-4 mb-4">Key Papers</h2><h3 class="text-lg leading-7 text-gray-600 tracking-tight mt-4 mb-4">These papers exemplify key current areas of research in the lab.</h3><div class="grid grid-cols-2 gap-4"><!--[--><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_carr.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex</h3><a href="https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Immunity. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_dadonaite_a.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades</h3><a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Nature. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_dadonaite_b.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance</h3><a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">bioRxiv. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_loes.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</h3><a href="https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">bioRxiv. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_bloom_c.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Fitness effects of mutations to SARS-CoV-2 proteins</h3><a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Virus Evolution. 2023</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_bacsik.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Influenza virus transcription and progeny production are poorly correlated in single cells</h3><a href="https://elifesciences.org/articles/86852" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">eLife. 2023</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_dadonaite_crawford_radford.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike</h3><a href="https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Cell. 2023</a></div></a></div><!--]--></div></div><div class="all-publications"><h2 class="text-3xl leading-8 font-bold text-gray-800 tracking-tight mt-4 mb-4">All Papers</h2><h3 class="text-lg leading-7 text-gray-600 tracking-tight mt-4 mb-4">Below is a complete list of primary research papers from our group.</h3><div class="flex"><ul class="flex-1 divide-y divide-gray-200"><!--[--><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_welsh.jpg" alt="Image for Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_welsh.html">Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Frances C Welsh, Rachel T Eguia, Juhye M Lee, Hugh K Haddox, Jared Galloway, Nguyen Van Vinh Chau, Andrea N Loes, John Huddleston, Timothy C Yu, Mai Quynh Le, Nguyen TD Nhat, Nguyen Thi Le Thanh, Alexander L Greninger, Helen Y Chu, Janet A Englund, Trevor Bedford, Frederick A Matsen IV, Maciej F Boni, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell Host &amp; Microbe</span>. 2024. <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6" target="_blank">doi:10.1016/j.chom.2024.06.015</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_welsh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_hannon.jpg" alt="Image for dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_hannon.html">dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets</a></h2><div class="max-w-none text-gray-700 hidden lg:block">William W Hannon, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of Open Source Software</span>. 2024. <a href="https://joss.theoj.org/papers/10.21105/joss.06129" target="_blank">doi:10.21105/joss.06129</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_hannon.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_carr.jpg" alt="Image for Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_carr.html">Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caleb R Carr*, Katharine HD Crawford*, Michael Murphy, Jared G Galloway, Hugh K Haddox, Frederick A Matsen, Kristian G Andersen, Neil P King, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Immunity</span>. 2024. <a href="https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4" target="_blank">doi:10.1016/j.immuni.2024.06.013</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_carr.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_dadonaite_a.jpg" alt="Image for Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_dadonaite_a.html">Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite, Jack Brown, Teagan E McMahon, Ariana G Farrell, Marlin D Figgins, Daniel Asarnow, Cameron Stewart, Jimin Lee, Jenni Logue, Trevor Bedford, Ben Murrell, Helen Y Chu, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature</span>. 2024. <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank">doi:10.1038/s41586-024-07636-1</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_dadonaite_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_dadonaite_b.png" alt="Image for Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_dadonaite_b.html">Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite, Jenny J Ahn, Jordan T Ort, Jin Yu, Colleen Furey, Annie Dosey, William W Hannon, Amy Vincent Baker, Richard J Webby, Neil P King, Yan Liu, Scott E Hensley, Thomas P Peacock, Louise H Moncla, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">bioRxiv</span>. 2024. <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank">doi:10.1101/2024.05.23.595634</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_dadonaite_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_larsen.jpg" alt="Image for Functional and antigenic landscape of the Nipah virus receptor binding protein" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_larsen.html">Functional and antigenic landscape of the Nipah virus receptor binding protein</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Brendan B Larsen, Teagan McMahon, Jack T Brown, Zhaoqian Wang, Caelan E Radford, James E Crowe, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">bioRxiv</span>. 2024. <a href="https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract" target="_blank">doi:10.1101/2024.04.17.589977</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_larsen.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_loes.jpg" alt="Image for High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_loes.html">High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Andrea N Loes, Rosario Araceli L Tarabi, John Huddleston, Lisa Touyon, Sook San Wong, Samuel MS Cheng, Nancy HL Leung, William W Hannon, Trevor Bedford, Sarah Cobey, Benjamin J Cowling, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">bioRxiv</span>. 2024. <a href="https://www.biorxiv.org/content/10.1101/2024.03.08.584176v1.abstract" target="_blank">doi:10.1101/2024.03.08.584176</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_loes.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_bloom.jpg" alt="Image for Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_bloom.html">Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2024. <a href="https://academic.oup.com/ve/article/10/1/vead089/7504441" target="_blank">doi:10.1093/ve/vead089</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_kikawa.jpg" alt="Image for The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_kikawa.html">The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caroline Kikawa, Catiana H Cartwright-Acar, Jackson B Stuart, Maya Contreras, Lisa M Levoir, Matthew J Evans, Jesse D Bloom, Leslie Goo</div><div class="max-w-none text-gray-500"><span class="italic">Journal of Virology</span>. 2023. <a href="https://journals.asm.org/doi/full/10.1128/jvi.01414-23" target="_blank">doi:10.1128/jvi.01414-23</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_kikawa.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_c.jpg" alt="Image for Fitness effects of mutations to SARS-CoV-2 proteins" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_c.html">Fitness effects of mutations to SARS-CoV-2 proteins</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom, Richard A Neher</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2023. <a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank">doi:10.1093/ve/veae026</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_c.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bacsik.jpg" alt="Image for Influenza virus transcription and progeny production are poorly correlated in single cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bacsik.html">Influenza virus transcription and progeny production are poorly correlated in single cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">David J Bacsik, Bernadeta Dadonaite, Andrew Butler, Allison J Greaney, Nicholas S Heaton, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2023. <a href="https://elifesciences.org/articles/86852" target="_blank">doi:10.7554/eLife.86852.2</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bacsik.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_radford.png" alt="Image for Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_radford.html">Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caelan E Radford, Philipp Schommers, Lutz Gieselmann, Katharine HD Crawford, Bernadeta Dadonaite, Timothy C Yu, Adam S Dingens, Julie Overbaugh, Florian Klein, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell Host &amp; Microbe</span>. 2023. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf" target="_blank">doi:10.1016/j.chom.2023.05.025</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_radford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_a.jpg" alt="Image for Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_a.html">Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2023. <a href="https://academic.oup.com/ve/article/9/2/vead050/7249794" target="_blank">doi:10.1093/ve/vead050</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_b.jpg" alt="Image for Evolution of the SARS-CoV-2 mutational spectrum" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_b.html">Evolution of the SARS-CoV-2 mutational spectrum</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris</div><div class="max-w-none text-gray-500"><span class="italic">Molecular Biology and Evolution</span>. 2023. <a href="https://academic.oup.com/mbe/article/40/4/msad085/7113660" target="_blank">doi:10.1093/molbev/msad085</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_dadonaite_crawford_radford.png" alt="Image for A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_dadonaite_crawford_radford.html">A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite*, Katharine HD Crawford*, Caelan E Radford*, Ariana G Farrell, C Yu Timothy, William W Hannon, Panpan Zhou, Raiees Andrabi, Dennis R Burton, Lihong Liu, David D Ho, Helen Y Chu, Richard A Neher, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell</span>. 2023. <a href="https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf" target="_blank">doi:10.1016/j.cell.2023.02.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_dadonaite_crawford_radford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_greaney_a.png" alt="Image for Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_greaney_a.html">Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr*, Allison J Greaney*, Cameron M Stewart, Alexandra C Walls, William W Hannon, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951" target="_blank">doi:10.1371/journal.ppat.1010951</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_starr_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_farrell.png" alt="Image for Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_farrell.html">Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Ariana Ghez Farrell*, Bernadeta Dadonaite*, Allison J Greaney, Rachel Eguia, Andrea N Loes, Nicholas M Franko, Jennifer Logue, Juan Manuel Carreño, Anass Abbad, Helen Y Chu, Kenneth A Matreyek, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2022. <a href="https://www.mdpi.com/1999-4915/14/9/2061" target="_blank">doi:10.3390/v14092061</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_farrell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_greaney_b.jpg" alt="Image for Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_greaney_b.html">Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr*, Allison J Greaney*, William W Hannon, Andrea N Loes, Kevin Hauser, Josh R Dillen, Elena Ferri, Ariana Ghez Farrell, Bernadeta Dadonaite, Matthew McCallum, Kenneth A Matreyek, Davide Corti, David Veesler, Gyorgy Snell, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Science</span>. 2022. <a href="https://www.science.org/doi/full/10.1126/science.abo7896" target="_blank">doi:10.1126/science.abo7896</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_starr_greaney_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_hannon.jpg" alt="Image for Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_hannon.html">Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat</a></h2><div class="max-w-none text-gray-700 hidden lg:block">William W Hannon, Pavitra Roychoudhury, Hong Xie, Lasata Shrestha, Amin Addetia, Keith R Jerome, Alexander L Greninger, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2022. <a href="https://academic.oup.com/ve/article/8/2/veac052/6609212" target="_blank">doi:10.1093/ve/veac052</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_hannon.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_yu.jpg" alt="Image for A biophysical model of viral escape from polyclonal antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_yu.html">A biophysical model of viral escape from polyclonal antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Timothy C Yu, Zorian T Thornton, William W Hannon, William S DeWitt, Caelan E Radford, Frederick A Matsen IV, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2022. <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank">doi:10.1093/ve/veac110</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_yu.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_a.png" alt="Image for The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_greaney_a.html">The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Rachel T Eguia, Tyler N Starr, Khadija Khan, Nicholas Franko, Jennifer K Logue, Sandra M Lord, Cate Speake, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS Pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592" target="_blank">doi:10.1371/journal.ppat.1010592</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_a.jpg" alt="Image for ACE2 binding is an ancestral and evolvable trait of sarbecoviruses" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_a.html">ACE2 binding is an ancestral and evolvable trait of sarbecoviruses</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr, Samantha K Zepeda, Alexandra C Walls, Allison J Greaney, Sergey Alkhovsky, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature</span>. 2022. <a href="https://www.nature.com/articles/s41586-022-04464-z" target="_blank">doi:10.1038/s41586-022-04464-z</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_starr_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_b.png" alt="Image for A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_greaney_b.html">A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Tyler N Starr, Rachel T Eguia, Andrea N Loes, Khadija Khan, Farina Karim, Sandile Cele, John E Bowen, Jennifer K Logue, Davide Corti, David Veesler, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248" target="_blank">doi:10.1371/journal.ppat.1010248</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_greaney_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_gentles.jpg" alt="Image for Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_gentles.html">Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lauren E Gentles, Leanne Kehoe, Katharine HD Crawford, Kirsten Lacombe, Jane Dickerson, Caitlin Wolf, Joanna Yuan, Susanna Schuler, John T Watson, Sankan Nyanseor, Melissa Briggs-Hagen, Sharon Saydah, Claire M Midgley, Kimberly Pringle, Helen Chu, Jesse D Bloom, Janet A Englund</div><div class="max-w-none text-gray-500"><span class="italic">medRxiv</span>. 2022. <a href="https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1" target="_blank">doi:10.1101/2022.01.14.22269235</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_gentles.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_c.jpg" alt="Image for An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a 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data sheds more light on the early Wuhan SARS-CoV-2 epidemic" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_bloom_a.html">Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">mBio</span>. 2021. <a href="https://academic.oup.com/mbe/article/38/12/5211/6353034" target="_blank">doi:10.1093/molbev/msab246</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_bloom_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col 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Daniel Poston, Frauke Muecksch, Theodora Hatziioannou, Paul D Bieniasz, Davide F Robbiani, Michel C Nussenzweig, Pamela J Bjorkman, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature Communications</span>. 2021. <a href="https://www.nature.com/articles/s41467-021-24435-8" target="_blank">doi:10.1038/s41467-021-24435-8</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_greaney_b.jpg" alt="Image for Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection" class="w-full h-auto object-cover 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class="italic">Viruses</span>. 2021. <a href="https://www.mdpi.com/1999-4915/13/7/1196" target="_blank">doi:10.3390/v13071196</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_soh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_greaney_welsh.jpg" alt="Image for Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_greaney_welsh.html">Co-dominant neutralizing epitopes make 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object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_starr_b.html">Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr, Allison J Greaney, Adam S Dingens, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell Reports Medicine</span>. 2021. <a href="https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00071-9.pdf" target="_blank">doi:10.1016/j.xcrm.2021.100255</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_starr_b.html">Read more →</a></div></div></div></li><li class="py-12"><div 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href="/papers/2021_greaney_c.html">Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Andrea N Loes, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell host &amp; microbe</span>. 2021. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf" target="_blank">doi:10.1016/j.chom.2021.02.003</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_greaney_c.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_starr_greaney.jpg" alt="Image for Prospective mapping of viral mutations that escape antibodies used to treat COVID-19" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_starr_greaney.html">Prospective mapping of viral mutations that escape antibodies used to treat COVID-19</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr*, Allison J Greaney*, Amin Addetia, William W Hannon, Manish C Choudhary, Adam S Dingens, Jonathan Z Li, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Science</span>. 2021. <a href="https://www.science.org/doi/full/10.1126/science.abf9302" target="_blank">doi:10.1126/science.abf9302</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium 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HD Crawford, Adam S Dingens, Rachel S Nargi, Rachel E Sutton, Naveenchandra Suryadevara, Paul W Rothlauf, Zhuoming Liu, Sean PJ Whelan, Robert H Carnahan, James E Crowe, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell host &amp; microbe</span>. 2021. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30624-7.pdf" target="_blank">doi:10.1016/j.chom.2020.11.007</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_greaney_d.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_loes.jpg" alt="Image for Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice" class="w-full 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class="italic">Cell</span>. 2020. <a href="https://www.sciencedirect.com/science/article/pii/S0092867420310035?via%3Dihub" target="_blank">doi:10.1016/j.cell.2020.08.012</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_starr_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_dingens.jpg" alt="Image for Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_dingens.html">Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Katharine HD Crawford, Amanda Adler, Sarah L Steele, Kirsten Lacombe, Rachel Eguia, Fatima Amanat, Alexandra C Walls, Caitlin R Wolf, Michael Murphy, Deleah Pettie, Lauren Carter, Xuan Qin, Neil P King, David Veesler, Florian Krammer, Jane A Dickerson, Helen Y Chu, Janet A Englund, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature communications</span>. 2020. <a href="https://www.nature.com/articles/s41467-020-18178-1" target="_blank">doi:10.1038/s41467-020-18178-1</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_dingens.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_hilton.png" alt="Image for dms-view: Interactive visualization tool for deep mutational scanning data" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_hilton.html">dms-view: Interactive visualization tool for deep mutational scanning data</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Sarah K Hilton*, John Huddleston*, Allison Black, Khrystyna North, Adam S Dingens, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">JOSS</span>. 2020. <a href="https://joss.theoj.org/papers/10.21105/joss.02353" target="_blank">doi:10.21105/joss.02353</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_hilton.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_gentles.png" alt="Image for Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_gentles.html">Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lauren E Gentles, Hongquan Wan, Maryna C Eichelberger, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/6/597" target="_blank">doi:10.3390/v12060597</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_gentles.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_crawford.jpg" alt="Image for Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_crawford.html">Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katharine HD Crawford, Rachel Eguia, Adam S Dingens, Andrea N Loes, Keara D Malone, Caitlin R Wolf, Helen Y Chu, M Alejandra Tortorici, David Veesler, Michael Murphy, Deleah Pettie, Neil P King, Alejandro B Balazs, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/5/513" target="_blank">doi:10.3390/v12050513</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_crawford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_einav_b.png" alt="Image for When two are better than one: Modeling the mechanisms of antibody mixtures" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_einav_b.html">When two are better than one: Modeling the mechanisms of antibody mixtures</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tal Einav, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS computational biology</span>. 2020. <a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830" target="_blank">doi:10.1371/journal.pcbi.1007830</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base 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text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/2/241" target="_blank">doi:10.3390/v12020241</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_roop.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_xue.jpg" alt="Image for Linking influenza virus evolution within and between human hosts" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_xue.html">Linking influenza virus evolution within and between human hosts</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus evolution</span>. 2020. <a href="https://academic.oup.com/ve/article/6/1/veaa010/5739536" target="_blank">doi:10.1093/ve/veaa010</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_xue_a.jpg" alt="Image for Reconciling disparate estimates of viral genetic diversity during human influenza infections" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_xue_a.html">Reconciling disparate estimates of viral genetic diversity during human influenza infections</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature genetics</span>. 2019. <a href="https://www.nature.com/articles/s41588-019-0349-3" target="_blank">doi:10.1038/s41588-019-0349-3</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_xue_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_lee.jpg" alt="Image for Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_lee.html">Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Juhye M Lee, Rachel Eguia, Seth J Zost, Saket Choudhary, Patrick C Wilson, Trevor Bedford, Terry Stevens-Ayers, Michael Boeckh, Aeron C Hurt, Seema S Lakdawala, Scott E Hensley, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2019. <a href="https://elifesciences.org/articles/49324" target="_blank">doi:10.7554/eLife.49324</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium 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text-gray-500"><span class="italic">Journal of virology</span>. 2019. <a href="https://journals.asm.org/doi/full/10.1128/jvi.00500-19" target="_blank">doi:10.1128/jvi.00500-19</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_russell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_dingens_a.jpg" alt="Image for Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_dingens_a.html">Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Dana Arenz, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2019. <a href="https://www.mdpi.com/1999-4915/11/5/439" target="_blank">doi:10.3390/v11050439</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_dingens_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_soh.jpg" alt="Image for Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_soh.html">Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans</a></h2><div class="max-w-none text-gray-700 hidden lg:block">YQ Shirleen Soh, Louise H Moncla, Rachel Eguia, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2019. <a href="https://doi.org/10.7554/eLife.45079" target="_blank">doi:10.7554/eLife.45079</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_soh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_dingens_b.jpg" alt="Image for An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_dingens_b.html">An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Immunity</span>. 2019. <a href="https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub" target="_blank">doi:10.1016/j.immuni.2018.12.017</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_dingens_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_crawford.png" alt="Image for alignparse: A Python package for parsing complex features from high-throughput long-read sequencing" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_crawford.html">alignparse: A Python package for parsing complex features from high-throughput long-read sequencing</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katharine HD Crawford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">JOSS</span>. 2019. <a href="https://doi.org/10.21105%2Fjoss.01915" target="_blank">doi:10.21105/joss.01915</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_crawford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_machkovech.png" alt="Image for Comprehensive profiling of translation initiation in influenza virus infected cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_machkovech.html">Comprehensive profiling of translation initiation in influenza virus infected cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Heather M Machkovech, Jesse D Bloom, Arvind R Subramaniam</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2019. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518" target="_blank">doi:10.1371/journal.ppat.1007518</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_machkovech.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_xue_a.jpg" alt="Image for Within-host evolution of human influenza virus" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_xue_a.html">Within-host evolution of human influenza virus</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Louise H Moncla, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Trends in Microbiology</span>. 2018. <a href="https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X" target="_blank">doi:10.1016/j.tim.2018.02.007</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_xue_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_lee.jpg" alt="Image for Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_lee.html">Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Juhye M Lee, John Huddleston, Michael B Doud, Kathryn A Hooper, Nicholas C Wu, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PNAS</span>. 2018. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.1806133115" target="_blank">doi:10.1073/pnas.1806133115</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_lee.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_dingens.png" alt="Image for Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_dingens.html">Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Priyamvada Acharya, Hugh K Haddox, Reda Rawi, Kai Xu, Gwo-Yu Chuang, Hui Wei, Baoshan Zhang, John R Mascola, Bridget Carragher, Clinton S Potter, Julie Overbaugh, Peter D Kwong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2018. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159" target="_blank">doi:10.1371/journal.ppat.1007159</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_dingens.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_hilton.jpg" alt="Image for Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_hilton.html">Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Sarah K Hilton, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus evolution</span>. 2018. <a href="https://academic.oup.com/ve/article/4/2/vey033/5163287" target="_blank">doi:10.1093/ve/vey033</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_hilton.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_doud.jpg" alt="Image for How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_doud.html">How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud*, Juhye M Lee*, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature communications</span>. 2018. <a href="https://www.nature.com/articles/s41467-018-03665-3" target="_blank">doi:10.1038/s41467-018-03665-3</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_haddox.jpg" alt="Image for Mapping mutational effects along the evolutionary landscape of HIV envelope" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_haddox.html">Mapping mutational effects along the evolutionary landscape of HIV envelope</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Hugh K Haddox*, Adam S Dingens*, Sarah K Hilton, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2018. <a href="https://elifesciences.org/articles/34420" target="_blank">doi:10.7554/eLife.34420</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_haddox.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_xue_b.jpg" alt="Image for Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_xue_b.html">Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Alexander L Greninger, Ailyn Pérez-Osorio, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">MSphere</span>. 2018. <a href="https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17" target="_blank">doi:10.1128/mspheredirect.00552-17</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_xue_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_russell.jpg" alt="Image for Extreme heterogeneity of influenza virus infection in single cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_russell.html">Extreme heterogeneity of influenza virus infection in single cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Alistair B Russell, Cole Trapnell, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2018. <a href="https://elifesciences.org/articles/32303" target="_blank">doi:10.7554/eLife.32303</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_russell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_bloom.jpg" alt="Image for Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_bloom.html">Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Biology direct</span>. 2017. <a href="https://link.springer.com/article/10.1186/s13062-016-0172-z" target="_blank">doi:10.1186/s13062-016-0172-z</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_hilton.jpg" alt="Image for phydms: Software for phylogenetic analyses informed by deep mutational scanning" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_hilton.html">phydms: Software for phylogenetic analyses informed by deep mutational scanning</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Sarah K Hilton, Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PeerJ</span>. 2017. <a href="https://peerj.com/articles/3657/" target="_blank">doi:10.7717/peerj.3657</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_hilton.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_xue.jpg" alt="Image for Parallel evolution of influenza across multiple spatiotemporal scales" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_xue.html">Parallel evolution of influenza across multiple spatiotemporal scales</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Terry Stevens-Ayers, Angela P Campbell, Janet A Englund, Steven A Pergam, Michael Boeckh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2017. <a href="https://elifesciences.org/articles/26875" target="_blank">doi:10.7554/eLife.26875.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_dingens.jpg" alt="Image for Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_dingens.html">Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Hugh K Haddox, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell host &amp; microbe</span>. 2017. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf" target="_blank">doi:10.1016/j.chom.2017.05.003</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_dingens.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_ashenberg.png" alt="Image for Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_ashenberg.html">Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Orr Ashenberg, Jai Padmakumar, Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2017. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288" target="_blank">doi:10.1371/journal.ppat.1006288</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_ashenberg.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_doud.png" alt="Image for Complete mapping of viral escape from neutralizing antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_doud.html">Complete mapping of viral escape from neutralizing antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Scott E Hensley, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2017. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271" target="_blank">doi:10.1371/journal.ppat.1006271</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_haddox.png" alt="Image for Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_haddox.html">Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Hugh K Haddox, Adam S Dingens, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2016. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114" target="_blank">doi:10.1371/journal.ppat.1006114</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_haddox.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_doud.jpg" alt="Image for Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_doud.html">Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2016. <a href="https://www.mdpi.com/1999-4915/8/6/155" target="_blank">doi:10.3390/v8060155</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_xue.jpg" alt="Image for Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_xue.html">Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Kathryn A Hooper, Anja R Ollodart, Adam S Dingens, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2016. <a href="https://elifesciences.org/articles/13974" target="_blank">doi:10.7554/eLife.13974.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_bloom.jpg" alt="Image for Software for the analysis and visualization of deep mutational scanning data" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_bloom.html">Software for the analysis and visualization of deep mutational scanning data</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">BMC bioinformatics</span>. 2015. <a href="https://link.springer.com/article/10.1186/s12859-015-0590-4" target="_blank">doi:10.1186/s12859-015-0590-4</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_machkovech.jpg" alt="Image for Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_machkovech.html">Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Heather M Machkovech, Trevor Bedford, Marc A Suchard, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2015. <a href="https://journals.asm.org/doi/full/10.1128/jvi.01571-15" target="_blank">doi:10.1128/jvi.01571-15</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_machkovech.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_doud.jpg" alt="Image for Site-specific amino acid preferences are mostly conserved in two closely related protein homologs" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_doud.html">Site-specific amino acid preferences are mostly conserved in two closely related protein homologs</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Orr Ashenberg, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular biology and evolution</span>. 2015. <a href="https://academic.oup.com/mbe/article/32/11/2944/982113" target="_blank">doi:10.1093/molbev/msv167</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_hooper.jpg" alt="Image for Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_hooper.html">Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Kathryn A Hooper, James E Crowe Jr, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2015. <a href="https://journals.asm.org/doi/full/10.1128/jvi.00012-15" target="_blank">doi:10.1128/jvi.00012-15</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_hooper.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_bloom_a.jpg" alt="Image for An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_bloom_a.html">An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular biology and evolution</span>. 2014. <a href="https://academic.oup.com/mbe/article/31/10/2753/1015257" target="_blank">doi:10.1093/molbev/msu220</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_bloom_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_bloom_b.jpg" alt="Image for An experimentally determined evolutionary model dramatically improves phylogenetic fit" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_bloom_b.html">An experimentally determined evolutionary model dramatically improves phylogenetic fit</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular Biology and Evolution</span>. 2014. <a href="https://academic.oup.com/mbe/article/31/8/1956/2925795" target="_blank">doi:10.1093/molbev/msu173</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_bloom_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_thyagarajan.jpg" alt="Image for The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_thyagarajan.html">The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bargavi Thyagarajan, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2014. <a href="https://elifesciences.org/articles/3300" target="_blank">doi:10.7554/eLife.03300</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_thyagarajan.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_gong.png" alt="Image for Epistatically interacting substitutions are enriched during adaptive protein evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_gong.html">Epistatically interacting substitutions are enriched during adaptive protein evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lizhi Ian Gong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS genetics</span>. 2014. <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328" target="_blank">doi:10.1371/journal.pgen.1004328</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_gong.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2013_ashenberg.jpg" alt="Image for Mutational effects on stability are largely conserved during protein evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2013_ashenberg.html">Mutational effects on stability are largely conserved during protein evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Orr Ashenberg, Lizhi Ian Gong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PNAS</span>. 2013. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.1314781111" target="_blank">doi:10.1073/pnas.1314781111</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2013_ashenberg.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2013_hooper.jpg" alt="Image for A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2013_hooper.html">A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Kathryn A Hooper, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2013. <a href="https://journals.asm.org/doi/full/10.1128/jvi.01889-13" target="_blank">doi:10.1128/jvi.01889-13</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2013_hooper.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2013_gong.jpg" alt="Image for Stability-mediated epistasis constrains the evolution of an influenza protein" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2013_gong.html">Stability-mediated epistasis constrains the evolution of an influenza protein</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lizhi Ian Gong, Marc A Suchard, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2013. <a href="https://elifesciences.org/articles/631" target="_blank">doi:10.7554/eLife.00631.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2013_gong.html">Read more 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+    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="divide-y divide-gray-200"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14"> Papers </h1><p class="text-xl leading-8 text-gray-800"> Papers from the Bloom Lab team. See also <a href="https://scholar.google.com/citations?user=S12x_eQAAAAJ&amp;hl" target="_blank">Google Scholar</a> for a complete list of publications. </p><div class="p-multiselect p-component p-inputwrapper w-full md:w-80" style="" data-pc-name="multiselect" data-pc-section="root"><div class="p-hidden-accessible" data-pc-section="hiddeninputcontainer" data-p-hidden-accessible="true"><input type="text" readonly placeholder="Filter by Keywords" tabindex="0" role="combobox" aria-haspopup="listbox" aria-expanded="false" aria-controls="undefined_list" data-pc-section="hiddeninput"></div><div class="p-multiselect-label-container" data-pc-section="labelcontainer"><div class="p-multiselect-label p-placeholder" data-pc-section="label"><!--[--><!--[-->Filter by Keywords<!--]--><!--]--></div></div><div class="p-multiselect-dropdown" data-pc-section="dropdown"><!--[--><svg width="14" height="14" viewBox="0 0 14 14" fill="none" xmlns="http://www.w3.org/2000/svg" class="p-icon p-multiselect-dropdown-icon" aria-hidden="true" data-pc-section="dropdownicon"><path d="M7.01744 10.398C6.91269 10.3985 6.8089 10.378 6.71215 10.3379C6.61541 10.2977 6.52766 10.2386 6.45405 10.1641L1.13907 4.84913C1.03306 4.69404 0.985221 4.5065 1.00399 4.31958C1.02276 4.13266 1.10693 3.95838 1.24166 3.82747C1.37639 3.69655 1.55301 3.61742 1.74039 3.60402C1.92777 3.59062 2.11386 3.64382 2.26584 3.75424L7.01744 8.47394L11.769 3.75424C11.9189 3.65709 12.097 3.61306 12.2748 3.62921C12.4527 3.64535 12.6199 3.72073 12.7498 3.84328C12.8797 3.96582 12.9647 4.12842 12.9912 4.30502C13.0177 4.48162 12.9841 4.662 12.8958 4.81724L7.58083 10.1322C7.50996 10.2125 7.42344 10.2775 7.32656 10.3232C7.22968 10.3689 7.12449 10.3944 7.01744 10.398Z" fill="currentColor"></path></svg><!--]--></div><!----></div></div><div class="selected-publications mb-8"><h2 class="text-3xl leading-8 font-bold text-gray-800 tracking-tight mt-4 mb-4">Key Papers</h2><h3 class="text-lg leading-7 text-gray-600 tracking-tight mt-4 mb-4">These papers exemplify key current areas of research in the lab.</h3><div class="grid grid-cols-2 gap-4"><!--[--><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_loes.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</h3><a href="https://doi.org/10.1128/jvi.00689-24" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Journal of Virology. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_carr.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex</h3><a href="https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Immunity. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_dadonaite_a.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades</h3><a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Nature. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2024_dadonaite_b.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance</h3><a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">bioRxiv. 2024</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_bloom_c.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Fitness effects of mutations to SARS-CoV-2 proteins</h3><a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Virus Evolution. 2023</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_bacsik.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">Influenza virus transcription and progeny production are poorly correlated in single cells</h3><a href="https://elifesciences.org/articles/86852" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">eLife. 2023</a></div></a></div><div class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><a href="/papers/2023_dadonaite_crawford_radford.html" class="flex-grow bg-custom-soft no-underline p-4"><div class=""><h3 class="m-0 text-gray-800 font-semibold text-lg leading-6 ease-in-out pb-2">A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike</h3><a href="https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf" target="_blank" class="m-0 font-medium text-gray-600 pt-1 text-base no-underline">Cell. 2023</a></div></a></div><!--]--></div></div><div class="all-publications"><h2 class="text-3xl leading-8 font-bold text-gray-800 tracking-tight mt-4 mb-4">All Papers</h2><h3 class="text-lg leading-7 text-gray-600 tracking-tight mt-4 mb-4">Below is a complete list of primary research papers from our group.</h3><div class="flex"><ul class="flex-1 divide-y divide-gray-200"><!--[--><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_loes.jpg" alt="Image for High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_loes.html">High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Andrea N Loes, Rosario Araceli L Tarabi, John Huddleston, Lisa Touyon, Sook San Wong, Samuel MS Cheng, Nancy HL Leung, William W Hannon, Trevor Bedford, Sarah Cobey, Benjamin J Cowling, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of Virology</span>. 2024. <a href="https://doi.org/10.1128/jvi.00689-24" target="_blank">doi:10.1128/jvi.00689-24</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_loes.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_welsh.jpg" alt="Image for Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_welsh.html">Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Frances C Welsh, Rachel T Eguia, Juhye M Lee, Hugh K Haddox, Jared Galloway, Nguyen Van Vinh Chau, Andrea N Loes, John Huddleston, Timothy C Yu, Mai Quynh Le, Nguyen TD Nhat, Nguyen Thi Le Thanh, Alexander L Greninger, Helen Y Chu, Janet A Englund, Trevor Bedford, Frederick A Matsen IV, Maciej F Boni, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell Host &amp; Microbe</span>. 2024. <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00233-6" target="_blank">doi:10.1016/j.chom.2024.06.015</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_welsh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_hannon.jpg" alt="Image for dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_hannon.html">dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets</a></h2><div class="max-w-none text-gray-700 hidden lg:block">William W Hannon, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of Open Source Software</span>. 2024. <a href="https://joss.theoj.org/papers/10.21105/joss.06129" target="_blank">doi:10.21105/joss.06129</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_hannon.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_carr.jpg" alt="Image for Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_carr.html">Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caleb R Carr*, Katharine HD Crawford*, Michael Murphy, Jared G Galloway, Hugh K Haddox, Frederick A Matsen, Kristian G Andersen, Neil P King, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Immunity</span>. 2024. <a href="https://www.cell.com/immunity/fulltext/S1074-7613(24)00319-4" target="_blank">doi:10.1016/j.immuni.2024.06.013</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_carr.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_dadonaite_a.jpg" alt="Image for Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_dadonaite_a.html">Full-spike deep mutational scanning helps predict the evolutionary success of SARS-CoV-2 clades</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite, Jack Brown, Teagan E McMahon, Ariana G Farrell, Marlin D Figgins, Daniel Asarnow, Cameron Stewart, Jimin Lee, Jenni Logue, Trevor Bedford, Ben Murrell, Helen Y Chu, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature</span>. 2024. <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank">doi:10.1038/s41586-024-07636-1</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_dadonaite_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_dadonaite_b.png" alt="Image for Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_dadonaite_b.html">Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite, Jenny J Ahn, Jordan T Ort, Jin Yu, Colleen Furey, Annie Dosey, William W Hannon, Amy Vincent Baker, Richard J Webby, Neil P King, Yan Liu, Scott E Hensley, Thomas P Peacock, Louise H Moncla, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">bioRxiv</span>. 2024. <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank">doi:10.1101/2024.05.23.595634</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_dadonaite_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_larsen.jpg" alt="Image for Functional and antigenic landscape of the Nipah virus receptor binding protein" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_larsen.html">Functional and antigenic landscape of the Nipah virus receptor binding protein</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Brendan B Larsen, Teagan McMahon, Jack T Brown, Zhaoqian Wang, Caelan E Radford, James E Crowe, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">bioRxiv</span>. 2024. <a href="https://www.biorxiv.org/content/10.1101/2024.04.17.589977v1.abstract" target="_blank">doi:10.1101/2024.04.17.589977</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_larsen.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2024_bloom.jpg" alt="Image for Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2024_bloom.html">Importance of quantifying the number of viral reads in metagenomic sequencing of environmental samples from the Huanan Seafood Market</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2024. <a href="https://academic.oup.com/ve/article/10/1/vead089/7504441" target="_blank">doi:10.1093/ve/vead089</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2024_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_kikawa.jpg" alt="Image for The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_kikawa.html">The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caroline Kikawa, Catiana H Cartwright-Acar, Jackson B Stuart, Maya Contreras, Lisa M Levoir, Matthew J Evans, Jesse D Bloom, Leslie Goo</div><div class="max-w-none text-gray-500"><span class="italic">Journal of Virology</span>. 2023. <a href="https://journals.asm.org/doi/full/10.1128/jvi.01414-23" target="_blank">doi:10.1128/jvi.01414-23</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_kikawa.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_c.jpg" alt="Image for Fitness effects of mutations to SARS-CoV-2 proteins" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_c.html">Fitness effects of mutations to SARS-CoV-2 proteins</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom, Richard A Neher</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2023. <a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank">doi:10.1093/ve/veae026</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_c.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bacsik.jpg" alt="Image for Influenza virus transcription and progeny production are poorly correlated in single cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bacsik.html">Influenza virus transcription and progeny production are poorly correlated in single cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">David J Bacsik, Bernadeta Dadonaite, Andrew Butler, Allison J Greaney, Nicholas S Heaton, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2023. <a href="https://elifesciences.org/articles/86852" target="_blank">doi:10.7554/eLife.86852.2</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bacsik.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_radford.png" alt="Image for Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_radford.html">Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Caelan E Radford, Philipp Schommers, Lutz Gieselmann, Katharine HD Crawford, Bernadeta Dadonaite, Timothy C Yu, Adam S Dingens, Julie Overbaugh, Florian Klein, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell Host &amp; Microbe</span>. 2023. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(23)00218-4.pdf" target="_blank">doi:10.1016/j.chom.2023.05.025</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_radford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_a.jpg" alt="Image for Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_a.html">Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2023. <a href="https://academic.oup.com/ve/article/9/2/vead050/7249794" target="_blank">doi:10.1093/ve/vead050</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_bloom_b.jpg" alt="Image for Evolution of the SARS-CoV-2 mutational spectrum" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_bloom_b.html">Evolution of the SARS-CoV-2 mutational spectrum</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris</div><div class="max-w-none text-gray-500"><span class="italic">Molecular Biology and Evolution</span>. 2023. <a href="https://academic.oup.com/mbe/article/40/4/msad085/7113660" target="_blank">doi:10.1093/molbev/msad085</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_bloom_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2023_dadonaite_crawford_radford.png" alt="Image for A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2023_dadonaite_crawford_radford.html">A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bernadeta Dadonaite*, Katharine HD Crawford*, Caelan E Radford*, Ariana G Farrell, C Yu Timothy, William W Hannon, Panpan Zhou, Raiees Andrabi, Dennis R Burton, Lihong Liu, David D Ho, Helen Y Chu, Richard A Neher, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell</span>. 2023. <a href="https://www.cell.com/cell/pdf/S0092-8674(23)00103-4.pdf" target="_blank">doi:10.1016/j.cell.2023.02.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2023_dadonaite_crawford_radford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_greaney_a.png" alt="Image for Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_greaney_a.html">Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr*, Allison J Greaney*, Cameron M Stewart, Alexandra C Walls, William W Hannon, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010951" target="_blank">doi:10.1371/journal.ppat.1010951</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_starr_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_farrell.png" alt="Image for Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_farrell.html">Receptor-binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Ariana Ghez Farrell*, Bernadeta Dadonaite*, Allison J Greaney, Rachel Eguia, Andrea N Loes, Nicholas M Franko, Jennifer Logue, Juan Manuel Carreño, Anass Abbad, Helen Y Chu, Kenneth A Matreyek, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2022. <a href="https://www.mdpi.com/1999-4915/14/9/2061" target="_blank">doi:10.3390/v14092061</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_farrell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_greaney_b.jpg" alt="Image for Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_greaney_b.html">Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr*, Allison J Greaney*, William W Hannon, Andrea N Loes, Kevin Hauser, Josh R Dillen, Elena Ferri, Ariana Ghez Farrell, Bernadeta Dadonaite, Matthew McCallum, Kenneth A Matreyek, Davide Corti, David Veesler, Gyorgy Snell, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Science</span>. 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bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat</a></h2><div class="max-w-none text-gray-700 hidden lg:block">William W Hannon, Pavitra Roychoudhury, Hong Xie, Lasata Shrestha, Amin Addetia, Keith R Jerome, Alexander L Greninger, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2022. <a href="https://academic.oup.com/ve/article/8/2/veac052/6609212" target="_blank">doi:10.1093/ve/veac052</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_hannon.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_yu.jpg" alt="Image for A biophysical model of viral escape from polyclonal antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_yu.html">A biophysical model of viral escape from polyclonal antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Timothy C Yu, Zorian T Thornton, William W Hannon, William S DeWitt, Caelan E Radford, Frederick A Matsen IV, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2022. <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank">doi:10.1093/ve/veac110</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_yu.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_a.png" alt="Image for The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_greaney_a.html">The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Rachel T Eguia, Tyler N Starr, Khadija Khan, Nicholas Franko, Jennifer K Logue, Sandra M Lord, Cate Speake, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS Pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010592" target="_blank">doi:10.1371/journal.ppat.1010592</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_starr_a.jpg" alt="Image for ACE2 binding is an ancestral and evolvable trait of sarbecoviruses" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_starr_a.html">ACE2 binding is an ancestral and evolvable trait of sarbecoviruses</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr, Samantha K Zepeda, Alexandra C Walls, Allison J Greaney, Sergey Alkhovsky, David Veesler, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature</span>. 2022. <a href="https://www.nature.com/articles/s41586-022-04464-z" target="_blank">doi:10.1038/s41586-022-04464-z</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_starr_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_b.png" alt="Image for A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_greaney_b.html">A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Tyler N Starr, Rachel T Eguia, Andrea N Loes, Khadija Khan, Farina Karim, Sandile Cele, John E Bowen, Jennifer K Logue, Davide Corti, David Veesler, Helen Y Chu, Alex Sigal, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2022. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010248" target="_blank">doi:10.1371/journal.ppat.1010248</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_greaney_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_gentles.jpg" alt="Image for Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_gentles.html">Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lauren E Gentles, Leanne Kehoe, Katharine HD Crawford, Kirsten Lacombe, Jane Dickerson, Caitlin Wolf, Joanna Yuan, Susanna Schuler, John T Watson, Sankan Nyanseor, Melissa Briggs-Hagen, Sharon Saydah, Claire M Midgley, Kimberly Pringle, Helen Chu, Jesse D Bloom, Janet A Englund</div><div class="max-w-none text-gray-500"><span class="italic">medRxiv</span>. 2022. <a href="https://www.medrxiv.org/content/10.1101/2022.01.14.22269235v1" target="_blank">doi:10.1101/2022.01.14.22269235</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_gentles.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2022_greaney_c.jpg" alt="Image for An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2022_greaney_c.html">An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Tyler N Starr, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus Evolution</span>. 2022. <a href="https://academic.oup.com/ve/article/8/1/veac021/6549895" target="_blank">doi:10.1093/ve/veac021</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2022_greaney_c.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_bloom_a.jpg" alt="Image for Recovery of deleted deep sequencing 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md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_starr_greaney_a.jpg" alt="Image for SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_starr_greaney_a.html">SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tyler N Starr, Nadine Czudnochowski, Zhuoming Liu, Fabrizia Zatta, Young-Jun Park, Amin Addetia, Dora Pinto, Martina Beltramello, Patrick Hernandez, Allison J Greaney, Roberta Marzi, William G Glass, Ivy Zhang, Adam S Dingens, John E Bowen, M Alejandra Tortorici, Alexandra C Walls, Jason A Wojcechowskyj, Anna De Marco, Laura E Rosen, Jiayi Zhou, Martin Montiel-Ruiz, Hannah Kaiser, Josh R Dillen, Heather Tucker, Jessica Bassi, Chiara Silacci-Fregni, Michael P Housley, Julia di Iulio, Gloria Lombardo, Maria Agostini, Nicole Sprugasci, Katja Culap, Stefano Jaconi, Marcel Meury, Exequiel Dellota Jr, Rana Abdelnabi, Shi-Yan Caroline Foo, Elisabetta Cameroni, Spencer Stumpf, Tristan I Croll, Jay C Nix, Colin Havenar-Daughton, Luca Piccoli, Fabio Benigni, Johan Neyts, Amalio Telenti, Florian A Lempp, Matteo S Pizzuto, John D Chodera, Christy M Hebner, Herbert W Virgin, Sean PJ Whelan, David Veesler, Davide Corti, Jesse D Bloom, Gyorgy Snell</div><div class="max-w-none text-gray-500"><span class="italic">Nature</span>. 2021. <a href="https://www.nature.com/articles/s41586-021-03807-6" target="_blank">doi:10.1038/s41586-021-03807-6</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_starr_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_greaney_a.jpg" alt="Image for Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_greaney_a.html">Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Tyler N Starr, Christopher O Barnes, Yiska Weisblum, Fabian Schmidt, Marina Caskey, Christian Gaebler, Alice Cho, Marianna Agudelo, Shlomo Finkin, Zijun Wang, Daniel Poston, Frauke Muecksch, Theodora Hatziioannou, Paul D Bieniasz, Davide F Robbiani, Michel C Nussenzweig, Pamela J Bjorkman, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature Communications</span>. 2021. <a href="https://www.nature.com/articles/s41467-021-24435-8" target="_blank">doi:10.1038/s41467-021-24435-8</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_greaney_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_greaney_b.jpg" alt="Image for Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection" class="w-full h-auto object-cover 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class="italic">Viruses</span>. 2021. <a href="https://www.mdpi.com/1999-4915/13/7/1196" target="_blank">doi:10.3390/v13071196</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_soh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2021_greaney_welsh.jpg" alt="Image for Co-dominant neutralizing epitopes make anti-measles immunity resistant to viral evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2021_greaney_welsh.html">Co-dominant neutralizing epitopes make 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href="/papers/2021_greaney_c.html">Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Allison J Greaney, Andrea N Loes, Katharine HD Crawford, Tyler N Starr, Keara D Malone, Helen Y Chu, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell host &amp; microbe</span>. 2021. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(21)00082-2.pdf" target="_blank">doi:10.1016/j.chom.2021.02.003</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2021_greaney_c.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img 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hidden lg:block">Lauren E Gentles, Hongquan Wan, Maryna C Eichelberger, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/6/597" target="_blank">doi:10.3390/v12060597</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_gentles.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_crawford.jpg" alt="Image for Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_crawford.html">Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katharine HD Crawford, Rachel Eguia, Adam S Dingens, Andrea N Loes, Keara D Malone, Caitlin R Wolf, Helen Y Chu, M Alejandra Tortorici, David Veesler, Michael Murphy, Deleah Pettie, Neil P King, Alejandro B Balazs, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/5/513" target="_blank">doi:10.3390/v12050513</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_crawford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_einav_b.png" alt="Image for When two are better than one: Modeling the mechanisms of antibody mixtures" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_einav_b.html">When two are better than one: Modeling the mechanisms of antibody mixtures</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Tal Einav, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS computational biology</span>. 2020. <a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007830" target="_blank">doi:10.1371/journal.pcbi.1007830</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base 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text-gray-500"><span class="italic">Viruses</span>. 2020. <a href="https://www.mdpi.com/1999-4915/12/2/241" target="_blank">doi:10.3390/v12020241</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_roop.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2020_xue.jpg" alt="Image for Linking influenza virus evolution within and between human hosts" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2020_xue.html">Linking influenza virus evolution within and between human hosts</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus evolution</span>. 2020. <a href="https://academic.oup.com/ve/article/6/1/veaa010/5739536" target="_blank">doi:10.1093/ve/veaa010</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2020_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_xue_a.jpg" alt="Image for Reconciling disparate estimates of viral genetic diversity during human influenza infections" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_xue_a.html">Reconciling disparate estimates of viral genetic diversity during human influenza infections</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature genetics</span>. 2019. <a href="https://www.nature.com/articles/s41588-019-0349-3" target="_blank">doi:10.1038/s41588-019-0349-3</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_xue_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_lee.jpg" alt="Image for Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_lee.html">Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Juhye M Lee, Rachel Eguia, Seth J Zost, Saket Choudhary, Patrick C Wilson, Trevor Bedford, Terry Stevens-Ayers, Michael Boeckh, Aeron C Hurt, Seema S Lakdawala, Scott E Hensley, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2019. <a href="https://elifesciences.org/articles/49324" target="_blank">doi:10.7554/eLife.49324</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_lee.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_russell.jpg" alt="Image for Single-cell virus sequencing of influenza infections that trigger innate immunity" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_russell.html">Single-cell virus sequencing of influenza infections that trigger innate immunity</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Alistair B Russell, Elizaveta Elshina, Jacob R Kowalsky, Aartjan JW Te Velthuis, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2019. <a href="https://journals.asm.org/doi/full/10.1128/jvi.00500-19" target="_blank">doi:10.1128/jvi.00500-19</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_russell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_dingens_a.jpg" alt="Image for Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_dingens_a.html">Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Dana Arenz, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2019. <a href="https://www.mdpi.com/1999-4915/11/5/439" target="_blank">doi:10.3390/v11050439</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_dingens_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_soh.jpg" alt="Image for Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_soh.html">Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans</a></h2><div class="max-w-none text-gray-700 hidden lg:block">YQ Shirleen Soh, Louise H Moncla, Rachel Eguia, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2019. <a href="https://doi.org/10.7554/eLife.45079" target="_blank">doi:10.7554/eLife.45079</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_soh.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_dingens_b.jpg" alt="Image for An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_dingens_b.html">An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies distinguishes functional and structural epitopes</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Immunity</span>. 2019. <a href="https://www.sciencedirect.com/science/article/pii/S107476131830565X?via%3Dihub" target="_blank">doi:10.1016/j.immuni.2018.12.017</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_dingens_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_crawford.png" alt="Image for alignparse: A Python package for parsing complex features from high-throughput long-read sequencing" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_crawford.html">alignparse: A Python package for parsing complex features from high-throughput long-read sequencing</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katharine HD Crawford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">JOSS</span>. 2019. <a href="https://doi.org/10.21105%2Fjoss.01915" target="_blank">doi:10.21105/joss.01915</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_crawford.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2019_machkovech.png" alt="Image for Comprehensive profiling of translation initiation in influenza virus infected cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2019_machkovech.html">Comprehensive profiling of translation initiation in influenza virus infected cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Heather M Machkovech, Jesse D Bloom, Arvind R Subramaniam</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2019. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007518" target="_blank">doi:10.1371/journal.ppat.1007518</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2019_machkovech.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_xue_a.jpg" alt="Image for Within-host evolution of human influenza virus" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_xue_a.html">Within-host evolution of human influenza virus</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Louise H Moncla, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Trends in Microbiology</span>. 2018. <a href="https://www.cell.com/trends/microbiology/fulltext/S0966-842X(18)30043-X" target="_blank">doi:10.1016/j.tim.2018.02.007</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_xue_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_lee.jpg" alt="Image for Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_lee.html">Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Juhye M Lee, John Huddleston, Michael B Doud, Kathryn A Hooper, Nicholas C Wu, Trevor Bedford, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PNAS</span>. 2018. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.1806133115" target="_blank">doi:10.1073/pnas.1806133115</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_lee.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_dingens.png" alt="Image for Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_dingens.html">Complete functional mapping of infection-and vaccine-elicited antibodies against the fusion peptide of HIV</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Priyamvada Acharya, Hugh K Haddox, Reda Rawi, Kai Xu, Gwo-Yu Chuang, Hui Wei, Baoshan Zhang, John R Mascola, Bridget Carragher, Clinton S Potter, Julie Overbaugh, Peter D Kwong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2018. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007159" target="_blank">doi:10.1371/journal.ppat.1007159</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_dingens.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_hilton.jpg" alt="Image for Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_hilton.html">Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Sarah K Hilton, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Virus evolution</span>. 2018. <a href="https://academic.oup.com/ve/article/4/2/vey033/5163287" target="_blank">doi:10.1093/ve/vey033</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_hilton.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_doud.jpg" alt="Image for How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_doud.html">How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud*, Juhye M Lee*, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Nature communications</span>. 2018. <a href="https://www.nature.com/articles/s41467-018-03665-3" target="_blank">doi:10.1038/s41467-018-03665-3</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_haddox.jpg" alt="Image for Mapping mutational effects along the evolutionary landscape of HIV envelope" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_haddox.html">Mapping mutational effects along the evolutionary landscape of HIV envelope</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Hugh K Haddox*, Adam S Dingens*, Sarah K Hilton, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2018. <a href="https://elifesciences.org/articles/34420" target="_blank">doi:10.7554/eLife.34420</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_haddox.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_xue_b.jpg" alt="Image for Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_xue_b.html">Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Alexander L Greninger, Ailyn Pérez-Osorio, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">MSphere</span>. 2018. <a href="https://journals.asm.org/doi/full/10.1128/mspheredirect.00552-17" target="_blank">doi:10.1128/mspheredirect.00552-17</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_xue_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2018_russell.jpg" alt="Image for Extreme heterogeneity of influenza virus infection in single cells" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2018_russell.html">Extreme heterogeneity of influenza virus infection in single cells</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Alistair B Russell, Cole Trapnell, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2018. <a href="https://elifesciences.org/articles/32303" target="_blank">doi:10.7554/eLife.32303</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2018_russell.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_bloom.jpg" alt="Image for Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_bloom.html">Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Biology direct</span>. 2017. <a href="https://link.springer.com/article/10.1186/s13062-016-0172-z" target="_blank">doi:10.1186/s13062-016-0172-z</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_hilton.jpg" alt="Image for phydms: Software for phylogenetic analyses informed by deep mutational scanning" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_hilton.html">phydms: Software for phylogenetic analyses informed by deep mutational scanning</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Sarah K Hilton, Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PeerJ</span>. 2017. <a href="https://peerj.com/articles/3657/" target="_blank">doi:10.7717/peerj.3657</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_hilton.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_xue.jpg" alt="Image for Parallel evolution of influenza across multiple spatiotemporal scales" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_xue.html">Parallel evolution of influenza across multiple spatiotemporal scales</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Terry Stevens-Ayers, Angela P Campbell, Janet A Englund, Steven A Pergam, Michael Boeckh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2017. <a href="https://elifesciences.org/articles/26875" target="_blank">doi:10.7554/eLife.26875.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_dingens.jpg" alt="Image for Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_dingens.html">Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Adam S Dingens, Hugh K Haddox, Julie Overbaugh, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Cell host &amp; microbe</span>. 2017. <a href="https://www.cell.com/cell-host-microbe/pdf/S1931-3128(17)30196-8.pdf" target="_blank">doi:10.1016/j.chom.2017.05.003</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_dingens.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_ashenberg.png" alt="Image for Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_ashenberg.html">Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Orr Ashenberg, Jai Padmakumar, Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2017. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006288" target="_blank">doi:10.1371/journal.ppat.1006288</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_ashenberg.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2017_doud.png" alt="Image for Complete mapping of viral escape from neutralizing antibodies" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2017_doud.html">Complete mapping of viral escape from neutralizing antibodies</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Scott E Hensley, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2017. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006271" target="_blank">doi:10.1371/journal.ppat.1006271</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2017_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_haddox.png" alt="Image for Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_haddox.html">Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Hugh K Haddox, Adam S Dingens, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS pathogens</span>. 2016. <a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006114" target="_blank">doi:10.1371/journal.ppat.1006114</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_haddox.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_doud.jpg" alt="Image for Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_doud.html">Accurate measurement of the effects of all amino-acid mutations on influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Viruses</span>. 2016. <a href="https://www.mdpi.com/1999-4915/8/6/155" target="_blank">doi:10.3390/v8060155</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2016_xue.jpg" alt="Image for Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2016_xue.html">Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Katherine S Xue, Kathryn A Hooper, Anja R Ollodart, Adam S Dingens, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2016. <a href="https://elifesciences.org/articles/13974" target="_blank">doi:10.7554/eLife.13974.001</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2016_xue.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_bloom.jpg" alt="Image for Software for the analysis and visualization of deep mutational scanning data" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_bloom.html">Software for the analysis and visualization of deep mutational scanning data</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">BMC bioinformatics</span>. 2015. <a href="https://link.springer.com/article/10.1186/s12859-015-0590-4" target="_blank">doi:10.1186/s12859-015-0590-4</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_bloom.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_machkovech.jpg" alt="Image for Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_machkovech.html">Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Heather M Machkovech, Trevor Bedford, Marc A Suchard, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2015. <a href="https://journals.asm.org/doi/full/10.1128/jvi.01571-15" target="_blank">doi:10.1128/jvi.01571-15</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_machkovech.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_doud.jpg" alt="Image for Site-specific amino acid preferences are mostly conserved in two closely related protein homologs" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_doud.html">Site-specific amino acid preferences are mostly conserved in two closely related protein homologs</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Michael B Doud, Orr Ashenberg, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular biology and evolution</span>. 2015. <a href="https://academic.oup.com/mbe/article/32/11/2944/982113" target="_blank">doi:10.1093/molbev/msv167</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_doud.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2015_hooper.jpg" alt="Image for Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2015_hooper.html">Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in several lineages and show no attenuation in cell culture or mice</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Kathryn A Hooper, James E Crowe Jr, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Journal of virology</span>. 2015. <a href="https://journals.asm.org/doi/full/10.1128/jvi.00012-15" target="_blank">doi:10.1128/jvi.00012-15</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2015_hooper.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_bloom_a.jpg" alt="Image for An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_bloom_a.html">An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular biology and evolution</span>. 2014. <a href="https://academic.oup.com/mbe/article/31/10/2753/1015257" target="_blank">doi:10.1093/molbev/msu220</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_bloom_a.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_bloom_b.jpg" alt="Image for An experimentally determined evolutionary model dramatically improves phylogenetic fit" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_bloom_b.html">An experimentally determined evolutionary model dramatically improves phylogenetic fit</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">Molecular Biology and Evolution</span>. 2014. <a href="https://academic.oup.com/mbe/article/31/8/1956/2925795" target="_blank">doi:10.1093/molbev/msu173</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_bloom_b.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_thyagarajan.jpg" alt="Image for The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_thyagarajan.html">The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Bargavi Thyagarajan, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">eLife</span>. 2014. <a href="https://elifesciences.org/articles/3300" target="_blank">doi:10.7554/eLife.03300</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_thyagarajan.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2014_gong.png" alt="Image for Epistatically interacting substitutions are enriched during adaptive protein evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2014_gong.html">Epistatically interacting substitutions are enriched during adaptive protein evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Lizhi Ian Gong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PLoS genetics</span>. 2014. <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004328" target="_blank">doi:10.1371/journal.pgen.1004328</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2014_gong.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2013_ashenberg.jpg" alt="Image for Mutational effects on stability are largely conserved during protein evolution" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 text-xl md:text-2xl no-underline" href="/papers/2013_ashenberg.html">Mutational effects on stability are largely conserved during protein evolution</a></h2><div class="max-w-none text-gray-700 hidden lg:block">Orr Ashenberg, Lizhi Ian Gong, Jesse D Bloom</div><div class="max-w-none text-gray-500"><span class="italic">PNAS</span>. 2013. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.1314781111" target="_blank">doi:10.1073/pnas.1314781111</a></div></div><div class="mt-4 md:mt-0 md:self-end"><a class="text-base leading-6 font-medium text-custom-orange no-underline" aria-label="read more about {{ paper.title }}" href="/papers/2013_ashenberg.html">Read more →</a></div></div></div></li><li class="py-12"><div class="flex flex-col md:flex-row items-start"><div class="hidden md:block md:flex-none lg:w-48 lg:h-48 md:w-32 md:h-32 md:mr-4"><img src="/assets/papers/2013_hooper.jpg" alt="Image for A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein" class="w-full h-auto object-cover rounded-lg"></div><div class="space-y-5 md:flex-grow"><div class="space-y-2"><h2 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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/andrea-loes.jpg" alt="Andrea Loes" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Andrea Loes</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Staff Scientist/Lab Manager</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Andrea Loes, PhD is a staff scientist/lab manager for the Bloom Lab. She recently developed a high-throughput, sequencing-based method for running neutralization assays for influenza viruses and is currently applying this method to better understand the sources of diversity in the specificity of human serum antibodies to influenza viruses between different individuals.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/andrew-butler.jpg" alt="Andrew Butler" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Andrew Butler</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-website" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a postdoc in the Bloom Lab, I am interested in developing and applying single-cell methods to better understand heterogeneity in the context of viral infections.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/arjun-aditham.jpg" alt="Arjun Aditham" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Arjun Aditham</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a postdoc in the Bloom Lab, I&#39;m utilizing deep mutational scanning approaches to characterize the Rabies glycoprotein.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/bernadeta-dadonaite.jpg" alt="Bernadeta Dadonaite" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Bernadeta Dadonaite</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Staff Scientist</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Bernadeta is a staff scientist in the Bloom lab and works on deep mutational scanning of SARS-CoV-2 spike and H5 hemagglutinin.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/brendan-larsen.jpg" alt="Brendan Larsen" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Brendan Larsen</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-website" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Brendan Larsen is a Postdoctoral Fellow in the Bloom lab, where he studies the functional and antigenic evolution of Nipah virus. He is broadly interested in zoonotic viruses, in particular, bat and rodent-borne viruses that could potentially spillover into humans. He is funded by the Washington Research Foundation.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/caelan-radford.jpg" alt="Caelan Radford" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Caelan Radford</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Staff Scientist</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/caleb-carr.jpg" alt="Caleb Carr" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Caleb Carr</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a graduate student in the Bloom lab, I am using our deep mutational scanning (DMS) pipeline to study the glycoprotein complex of Lassa virus.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/caroline-kikawa.jpg" alt="Caroline Kikawa" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Caroline Kikawa</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>I&#39;m a graduate student in the Bloom lab using high-throughput sequencing-based neutralization assays to profile human neutralizing antibody responses to seasonal influenza viruses. More broadly, I&#39;m interested in understanding factors that impact influenza virus antigenic evolution and methods to improve forecasting.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/cassandra-simonich.jpg" alt="Cassandra Simonich" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Cassandra Simonich</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Pediatric Infectious Disease Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Cassie Simonich, MD, PhD is a Pediatric Infectious Diseases Fellow at Seattle Children’s Hospital. In the Bloom Lab, she studies the antigenic evolution of Respiratory Syncytial Virus.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/catherine-jacob-dolan.jpg" alt="Catherine Jacob-Dolan" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Catherine Jacob-Dolan</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Catherine is a new Postdoctoral Fellow in the Bloom lab.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14"> Meet the Team </h1></div><div class="w-full border-t border-gray-200"></div><!--[--><div class="category-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-xl leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Faculty</h1></div><div class="count-1"><div class="md:max-w-sm mx-auto max-w-sm grid grid-cols-1 md:grid-cols-[repeat(auto-fit,minmax(14rem,1fr))] gap-6"><!--[--><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/jesse-bloom.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/jesse-bloom.jpg" alt="Jesse Bloom"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Jesse Bloom</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Principal Investigator</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-scholar" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-orcid" /></div><!--]--><!--]--></div></div></div></article></div><!--]--></div></div></div><div class="category-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-xl leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Grad Students</h1></div><div class="count-6"><div class="md:max-w-7xl mx-auto max-w-sm grid grid-cols-1 md:grid-cols-[repeat(auto-fit,minmax(14rem,1fr))] gap-6"><!--[--><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/caleb-carr.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/caleb-carr.jpg" alt="Caleb Carr"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Caleb Carr</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/caroline-kikawa.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/caroline-kikawa.jpg" alt="Caroline Kikawa"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Caroline Kikawa</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/jenny-ahn.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/jenny-ahn.jpg" alt="Jenny Ahn"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Jenny Ahn</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/lizzie-plender.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/lizzie-plender.jpg" alt="Lizzie Plender"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Lizzie Plender</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/lucas-kampman.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/lucas-kampman.jpg" alt="Lucas Kampman"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Lucas Kampman</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-orcid" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/tim-yu.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/tim-yu.jpg" alt="Tim Yu"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Tim Yu</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Graduate Student</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><!--]--></div></div></div><div class="category-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-xl leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Postdocs</h1></div><div class="count-9"><div class="md:max-w-7xl mx-auto max-w-sm grid grid-cols-1 md:grid-cols-[repeat(auto-fit,minmax(14rem,1fr))] gap-6"><!--[--><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/andrew-butler.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/andrew-butler.jpg" alt="Andrew Butler"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Andrew Butler</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-website" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/arjun-aditham.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/arjun-aditham.jpg" alt="Arjun Aditham"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Arjun Aditham</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/brendan-larsen.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/brendan-larsen.jpg" alt="Brendan Larsen"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Brendan Larsen</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-website" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/cassandra-simonich.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/cassandra-simonich.jpg" alt="Cassandra Simonich"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Cassandra Simonich</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Pediatric Infectious Disease Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/catherine-jacob-dolan.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/catherine-jacob-dolan.jpg" alt="Catherine Jacob-Dolan"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Catherine Jacob-Dolan</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/sara-sunshine.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/sara-sunshine.jpg" alt="Sara Sunshine"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Sara Sunshine</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/sheri-harari.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/sheri-harari.jpg" alt="Sheri Harari"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Sheri Harari</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/wenlin-ren.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/wenlin-ren.jpg" alt="Wenlin Ren"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Wenlin Ren</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/xiaohui-ju.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/xiaohui-ju.jpg" alt="Xiaohui Ju"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Xiaohui Ju</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Postdoctoral Fellow</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><!--]--></div></div></div><div class="category-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-xl leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Staff</h1></div><div class="count-5"><div class="md:max-w-7xl mx-auto max-w-sm grid grid-cols-1 md:grid-cols-[repeat(auto-fit,minmax(14rem,1fr))] gap-6"><!--[--><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/andrea-loes.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/andrea-loes.jpg" alt="Andrea Loes"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Andrea Loes</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Staff Scientist/Lab Manager</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/bernadeta-dadonaite.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/bernadeta-dadonaite.jpg" alt="Bernadeta Dadonaite"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Bernadeta Dadonaite</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Staff Scientist</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/caelan-radford.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/caelan-radford.jpg" alt="Caelan Radford"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Caelan Radford</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Staff Scientist</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/teagan-mcmahon.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/teagan-mcmahon.jpg" alt="Teagan McMahon"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Teagan McMahon</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Research Technician</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><div class="item"><article class="hover:shadow-lg hover:shadow-custom-orange flex flex-col gap-px rounded-lg w-full h-full overflow-hidden transition-shadow duration-300 ease-in-out"><div href="/people/will-hannon.html" class="py-6 px-4 sm:py-8 sm:px-6 flex-grow bg-custom-soft cursor-pointer"><figure class="relative shrink-0 mx-auto w-36 h-36 rounded-full overflow-hidden shadow"><img class="absolute inset-0 w-full h-full object-cover" src="/assets/people/will-hannon.jpg" alt="Will Hannon"></figure><div class="text-center pt-6"><h1 class="m-0 text-gray-800 font-semibold tracking-wide leading-7 text-lg ease-in-out">Will Hannon</h1><p class="m-0 font-medium text-gray-600 pt-1 text-base"><span>Data Scientist</span></p><!----><div class="flex justify-center h-14 m-[-1rem -4rem -3rem] pt-4 px-3"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></article></div><!--]--></div></div></div><!--]--></div><h1 class="text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14 border-t border-gray-200 pt-10"> Alumni </h1><!--[--><div><div class="alumni-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-lg leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Postdocs </h1></div><!--[--><div class="ml-4"><div class="font-bold">Tal Einav</div><div>2019 - 2023</div><div><a href='https://www.lji.org/labs/einav-lab/'>Assistant Professor</a> at the La Jolla Institute of Immunology in San Diego</div></div><div class="ml-4"><div class="font-bold">Tyler Starr</div><div>2018 - 2023</div><div><a href='https://starr.biochem.utah.edu/'>Assistant Professor</a> at the University of Utah</div></div><div class="ml-4"><div class="font-bold">Karen Barnard</div><div>2020 - 2021</div><div>Senior Medical Writer at Pfizer</div></div><div class="ml-4"><div class="font-bold">Alistair Russell</div><div>2014 - 2019</div><div><a href='https://www.russell-lab.com/'>Assistant Professor</a> at UCSD Division of Biological Sciences</div></div><div class="ml-4"><div class="font-bold">Shirleen Soh</div><div>2015 - 2019</div><div>Head of Academic Research at National Research Foundation, Singapore</div></div><div class="ml-4"><div class="font-bold">Jeremy Roop</div><div>2016 - 2019</div><div>Scientist at Berkeley Brewing Science</div></div><div class="ml-4"><div class="font-bold">Orr Ashenberg</div><div>2013 - 2017</div><div>Associate Director, Computational Biology at Broad Institute of MIT and Harvard</div></div><div class="ml-4"><div class="font-bold">Bargavi Thyagarajan</div><div>2011 - 2014</div><div>Scientific Project Manager at the Allen Institute for Brain Science</div></div><!--]--></div></div><div><div class="alumni-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-lg leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Graduate Students </h1></div><!--[--><div class="ml-4"><div class="font-bold">Frances Welsh</div><div>2019 - 2024</div><div>Research Scientist at Amazon</div></div><div class="ml-4"><div class="font-bold">David Bacsik</div><div>2017 - 2023</div><div>Finishing medical school</div></div><div class="ml-4"><div class="font-bold">Lauren Gentles</div><div>2016 - 2022</div><div>Scientist III at Thermo Fisher Scientific</div></div><div class="ml-4"><div class="font-bold">Allie Greaney</div><div>2016 - 2022</div><div>Internal medicine resident at UCSF</div></div><div class="ml-4"><div class="font-bold">Kate Crawford</div><div>2017 - 2021</div><div>Laboratory Medicine and Pathology resident at UW</div></div><div class="ml-4"><div class="font-bold">Sarah Hilton</div><div>2016 - 2020</div><div>Senior Scientist at Dyno Therapeutics</div></div><div class="ml-4"><div class="font-bold">Adam Dingens</div><div>2015 - 2019</div><div>Director building a 'stealth mode' biotech company</div></div><div class="ml-4"><div class="font-bold">Katherine Xue</div><div>2015 - 2019</div><div>Incoming <a href='https://katherinesxue.com/'>Assistant Professor</a> at the University of California, Irvine</div></div><div class="ml-4"><div class="font-bold">Juhye Lee</div><div>2015 - 2019</div><div>Resident at Massachusetts General Hospital</div></div><div class="ml-4"><div class="font-bold">Heather Machkovech</div><div>2014 - 2018</div><div>Internal Medicine resident at University of Wisconsin Hospital and Clinic</div></div><div class="ml-4"><div class="font-bold">Hugh Haddox</div><div>2013 - 2017</div><div>Project Manager in Erick Matsen's lab at Fred Hutch</div></div><div class="ml-4"><div class="font-bold">Mike Doud</div><div>2013 - 2017</div><div>Infectious Disease Fellow at UC San Diego Health</div></div><div class="ml-4"><div class="font-bold">Kathryn Hooper</div><div>2012 - 2015</div><div>Senior Scientist at Sonoma Biotherapeutics</div></div><!--]--></div></div><div><div class="alumni-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-lg leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Staff Members </h1></div><!--[--><div class="ml-4"><div class="font-bold">Ariana Farrell</div><div>2020 - 2023</div><div>Incoming PhD student at UW Molecular and Cellular Biology</div></div><div class="ml-4"><div class="font-bold">Rosario Tarabi</div><div>2020 - 2024</div><div>Business student at Franciscan University of Steubenville</div></div><div class="ml-4"><div class="font-bold">Rachel Eguia</div><div>2019 - 2021</div><div>Associate Scientist at Variant Bio</div></div><div class="ml-4"><div class="font-bold">Keara Malone</div><div>2019 - 2021</div><div>Teaching English in Tochigi Prefecture, Japan</div></div><div class="ml-4"><div class="font-bold">Ian Gong</div><div>2011 - 2014</div><div>Assistant Facility Manager at Stop & Shop</div></div><!--]--></div></div><div><div class="alumni-section my-6"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-lg leading-9 font-bold text-gray-800 tracking-tight text-center md:text-left sm:text-2xl sm:leading-10 md:text-4xl md:leading-14">Undergraduate Researchers </h1></div><!--[--><div class="ml-4"><div class="font-bold">Jonathan Mah</div><div>2018 - 2020</div><!----></div><div class="ml-4"><div class="font-bold">Cameron Meikle</div><div>2018 - 2018</div><!----></div><div class="ml-4"><div class="font-bold">Noah Cassidy</div><div>2017 - 2018</div><!----></div><div class="ml-4"><div class="font-bold">Jacob Kowalsky</div><div>2016 - 2018</div><!----></div><div class="ml-4"><div class="font-bold">Alexandria Wilson</div><div>2017 - 2017</div><!----></div><div class="ml-4"><div class="font-bold">Jai Padmakumar</div><div>2014 - 2016</div><!----></div><div class="ml-4"><div class="font-bold">Lessane Ketema</div><div>2016 - 2016</div><!----></div><div class="ml-4"><div class="font-bold">Alex Heckert</div><div>2014 - 2015</div><!----></div><div class="ml-4"><div class="font-bold">Khrystyna Dilai</div><div>2014 - 2014</div><!----></div><div class="ml-4"><div class="font-bold">Kendra Ferrier</div><div>2014 - 2014</div><!----></div><div class="ml-4"><div class="font-bold">Brandon Pratt</div><div>2014 - 2014</div><!----></div><div class="ml-4"><div class="font-bold">Donna Leet</div><div>2012 - 2013</div><!----></div><div class="ml-4"><div class="font-bold">Ari Kaufman</div><div>2013 - 2013</div><!----></div><div class="ml-4"><div class="font-bold">Sam Schetterer</div><div>2011 - 2012</div><!----></div><!--]--></div></div><!--]--><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/jenny-ahn.jpg" alt="Jenny Ahn" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Jenny Ahn</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a Graduate student in the Bloom lab, I am using deep mutational scanning to study the evolution of pandemic potential avian influenza. I am interested in looking at how viruses evolve to improve our response to viral surveillance, vaccine development, and antibody engineering.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/jesse-bloom.jpg" alt="Jesse Bloom" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Jesse Bloom</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Principal Investigator</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-scholar" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-orcid" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Jesse is a professor at the Fred Hutchinson Cancer Research Center and an Investigator the Howard Hughes Medical Institute. Jesse started his lab at the Fred Hutch in 2011. Prior to that, he received a BS in Biological Chemistry from the University of Chicago (where he worked with Susan Lindquist), a MPhil in Theoretical Chemistry from Cambridge University (where he worked with David Wales), a PhD in Chemistry from Caltech (where he worked with Frances Arnold), and postdoctoral training in Biology at Caltech (where he worked with David Baltimore).</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/lizzie-plender.jpg" alt="Lizzie Plender" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Lizzie Plender</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Lizzie is a graduate student in the Bloom lab studying genetic variation in mucins, a group of innate immunity proteins that play critical roles in pathogen entrapment in health and disease.<br> Lizzie is joint-advised by <a href="https://eichlerlab.gs.washington.edu/index.html" target="_blank" rel="noreferrer">Evan Eichler</a>.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/lucas-kampman.jpg" alt="Lucas Kampman" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Lucas Kampman</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-orcid" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/sheri-harari.jpg" alt="Sheri Harari" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Sheri Harari</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-twitter" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Sheri is a postdoc in the Bloom Lab utilizing deep mutational scanning approaches to characterize the HCoV-229E spike glycoprotein.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/teagan-mcmahon.jpg" alt="Teagan McMahon" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Teagan McMahon</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Research Technician</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/tim-yu.jpg" alt="Tim Yu" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Tim Yu</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Graduate Student</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a graduate student in the Bloom lab, I use deep mutational scanning to help predict seasonal H3N2 influenza evolution.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/wenlin-ren.jpg" alt="Wenlin Ren" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Wenlin Ren</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>Wenlin is a postdoctoral researcher in the Bloom lab utilizing deep mutation scanning to investigate the entry mechanisms and antigenic evolution of coronaviruses and flaviviruses.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/will-hannon.jpg" alt="Will Hannon" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Will Hannon</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Data Scientist</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a Data Scientist in the Bloom Lab, I develop and implement computational approaches to study viral evolution and communicate with our data. I’m interested in improving access to the information-rich datasets we generate to aid in antigen engineering, therapeutic design, viral surveillance, and gaining a better understanding of viral evolution.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><!--[--><div class="header max-w-3xl py-8"><div class="flex flex-col lg:flex-row items-center text-center lg:text-left"><div class="flex-shrink-0 aspect-square w-32 h-32 bg-gray-200 rounded-full overflow-hidden"><img src="/assets/people/xiaohui-ju.jpg" alt="Xiaohui Ju" class="object-cover w-full h-full"></div><div class="mt-4 lg:mt-0 lg:ml-4"><h1 class="text-3xl lg:text-4xl leading-tight font-bold tracking-tight">Xiaohui Ju</h1><div class="mt-1"><h2 class="text-gray-600 font-light text-xl">Postdoctoral Fellow</h2></div><div class="inline-flex space-x-2 mt-1"><!--[--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-github" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-linkedin" /></div><!--]--><!--[--><!----><div class="flex justify-center items-center w-9 h-9 text-gray-600 transition-color duration-500 hover:text-custom-orange hover:duration-300"><span class="i-social-email" /></div><!--]--><!--]--></div></div></div></div><div class="prose"><!--[--><div style="position:relative;"><div><p>As a postdoc in Bloom Lab, I utilize deep mutational scanning approaches to characterize the Chikungunya virus envelope protein and non-structural protein in both vertebrate and invertebrate cells.</p></div></div><!--]--></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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+    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><h1>Deep mutational scanning of H5 influenza hemagglutinin</h1><!--[--><div style="position:relative;"><div><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>H5 influenza from clade 2.3.4.4b <a href="https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article" target="_blank" rel="noreferrer">has been causing</a> outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.</p><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study led by Bernadeta Dadonaite</a>, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.</p><p><img src="/assets/research/2024-05-25_h5-dms/phenotypes.jpg" alt="molecular phenotypes measured"></p><p>To make these measurements safely, we used a previously described <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus deep mutational scanning system</a> that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.</p><p><img src="/assets/research/2024-05-25_h5-dms/schematic.jpg" alt="pseudovirus schematic"></p><p>First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.</p><p><img src="/assets/research/2024-05-25_h5-dms/cell_entry_heatmap.jpg" alt="cell entry heatmap"><img src="/assets/research/2024-05-25_h5-dms/cell_entry_structure.jpg" alt="cell entry structure"></p><p>Next we measured how mutations affect HA&#39;s ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:</p><p><img src="/assets/research/2024-05-25_h5-dms/a2-6.jpg" alt="a2-6 usage"></p><p>We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:</p><p><img src="/assets/research/2024-05-25_h5-dms/stability.jpg" alt="stability"></p><p>Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:</p><p><img src="/assets/research/2024-05-25_h5-dms/escape.jpg" alt="escape"></p><p>To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see <a href="https://nextstrain.org/groups/moncla-lab/h5nx/2024-05-25_h5-dms/clade-2344b" target="_blank" rel="noreferrer">here</a> to color a phylogenetic tree by the measured phenotypes).</p><p>Angie Hinrichs <a href="https://x.com/AngieSHinrichs/status/1804270714570313873" target="_blank" rel="noreferrer">has also integrated the data into the UShER H5 trees</a>.</p><h2 id="how-to-visualize-and-access-the-data" tabindex="-1">How to visualize and access the data <a class="header-anchor" href="#how-to-visualize-and-access-the-data" aria-label="Permalink to &quot;How to visualize and access the data&quot;">​</a></h2><p>To make the data as accessible as possible for use by others, see</p><ul><li><p>An <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">interactive page</a> that allows you to visually examine heatmaps showing the effects of all the mutations on each measured phenotype.</p></li><li><p>An <a href="https://dms-viz.github.io/v0/?data=https%3A%2F%2Fraw.githubusercontent.com%2Fdms-vep%2FFlu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS%2Fmain%2Fresults%2Fdms-viz%2Fdms-viz.json" target="_blank" rel="noreferrer">interactive structure-based visualization</a></p></li><li><p>The <a href="https://github.com/dms-vep/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/blob/main/results/summaries/phenotypes.csv" target="_blank" rel="noreferrer">numerical values of the measurements</a> available.</p></li><li><p>Note that there are multiple HA numbering schemes in use, so make sure <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/numbering.html" target="_blank" rel="noreferrer">you understand how the mutations are being numbered</a>.</p></li></ul><h2 id="see-also" tabindex="-1">See also <a class="header-anchor" href="#see-also" aria-label="Permalink to &quot;See also&quot;">​</a></h2><p>See also <a href="https://x.com/jbloom_lab/status/1794364494858346803" target="_blank" rel="noreferrer">Jesse&#39;s Twitter thread</a> and <a href="https://slides.com/jbloom/h5-dms-short" target="_blank" rel="noreferrer">some slides about the study</a>.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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+    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><h1>Sequencing-based neutralization assays for influenza</h1><!--[--><div style="position:relative;"><div><p>In <a href="https://doi.org/10.1128/jvi.00689-24" target="_blank" rel="noreferrer">a paper</a> just published in <em>Journal of Virology</em>, we describe a new sequencing-based neutralization assay that dramatically increases the scale at which it is possible to measure how sera or antibodies neutralize different influenza virus strains.</p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>Neutralization assays are central to studying viral immunity. These assays involve making dilutions of serum, adding virus and cells, and then quantifying how much each serum dilution inhibits viral infection. The traditional readout is GFP fluorescence, luciferase, or plaques. Such readouts allow one virus to be analyzed per row or column of a 96-well plate, meaning that a single plate can be used to measure titers for at most 8 to 12 different serum-virus pairs. This limited throughput is a real problem when studying an antigenically variable virus like influenza, where we may want know neutralization titers against dozens or even hundreds of different viral strains.</p><p><a href="https://doi.org/10.1128/jvi.00689-24" target="_blank" rel="noreferrer">Our paper</a> describes a new approach spearheaded by Andrea Loes in our group that can measure titers for hundreds (or even up to a thousand) serum-virus pairs per 96-well plate, as shown below.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/per_plate.jpg" alt="measurements per plate"></p><p>How do we do this? The essence of our approach is to barcode each influenza virus strain, then combine all of the viruses and read out neutralization by all the viruses at once by deep sequencing, as schematized below. So it&#39;s like a traditional neutralization assay, except we measure all the viruses at once, rather than one at a time.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/schematic.jpg" alt="schematic of sequencing-based neutralization"></p><p>Below are some representative neutralization curves from the sequencing-based assay. They are identical to curves from traditional one-virus versus one-serum assays: the only difference is we generate replicate curves for hundreds of serum-virus pairs on each plate, rather than just a few curves per plate.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/example_curves.jpg" alt="example sequencing-based neutralization curves"></p><p>The neutralization titers measured using the sequencing-based assay are highly reproducible both across replicate barcodes for the same virus on the same plate, and across different plates run on different days, as shown below.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/correlations_within_assay.jpg" alt="correlations within assay"></p><p>The neutralization curves measured using the sequencing-based assay are also indistinguishable from those measured using a traditional fluorescence-based assay, as shown below:</p><p><img src="/assets/research/2024-09-24_flu_seqneut/correlations_with_traditional.jpg" alt="correlations with traditional"></p><p>We applied the assay to examine the response to repeated influenza vaccination, an important topic as <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00266-1/fulltext" target="_blank" rel="noreferrer">some studies</a> suggest reduced effectiveness of repeated vaccination. We analyzed samples from the <a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae380/7718587" target="_blank" rel="noreferrer">DRIVE study</a> led by Ben Cowling and Sarah Cobey. For each study participant at each timepoint, we used the sequencing-based neutralization assay to measure titers against 36 H1N1 strains (five vaccine strains plus 31 recent strains). So for each participant, we generate data like that shown below, which quantifies the pre- and post-vaccination titers against a wide range of recent viral strains.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/example_landscapes.jpg" alt="example neutralization landscapes"></p><p>In our sub-study (we only examined a fraction of all of the DRIVE samples), we looked at the response to the 2021-2022 vaccine in individual who had or had not been vaccinated in the prior year (2020-2021). Individuals who had <strong>not</strong> been vaccinated in the prior year (2020-2021) started with much lower pre-vaccination titers (purple points), but had a substantially larger marginal increase in titers after vaccination in 2021-2022 (red and green points) than individuals who had also been vaccinated the prior year. (This sort of makes sense: their starting titers were lower so there was more of an increase after vaccination.) The titers for the two groups are shown below:</p><p><img src="/assets/research/2024-09-24_flu_seqneut/vaccine_response.jpg" alt="vaccine response"></p><p>However, despite the larger marginal increase in titers for participants without prior-year vaccination, the final titers (especially at day 182) were similar among participants with and without a prior-year vaccination, since prior-year vaccinees started with higher titers.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/final_titers.jpg" alt="final titers"></p><p>Importantly, the participant-average plots above mask person- and virus-specific variation that probably has important implications for both influenza evolution and disease susceptibility (see plot below). Indeed, one of the things we are most excited about is using this new assay to extensively probe person-to-person variation in titers to different viral strains.</p><p><img src="/assets/research/2024-09-24_flu_seqneut/variation.jpg" alt="variation among viruses and individuals"></p><h2 id="want-to-use-this-approach-for-your-own-studies" tabindex="-1">Want to use this approach for your own studies? <a class="header-anchor" href="#want-to-use-this-approach-for-your-own-studies" aria-label="Permalink to &quot;Want to use this approach for your own studies?&quot;">​</a></h2><p>We think sequencing-based neutralization assays could be useful for a wide range of studies. To make the approach as accessible as possible for others, we have created:</p><ul><li><p>A publicly available <a href="https://github.com/jbloomlab/seqneut-pipeline" target="_blank" rel="noreferrer">computational pipeline</a> to analyze sequencing-based neutralization assay data. Note that this pipeline leverages an early <a href="https://jbloomlab.github.io/neutcurve/" target="_blank" rel="noreferrer">Python package we developed to fit neutralization curves</a>; the ability to automate the curve fitting becomes important when you are trying to analyze thousands of neutralization curves per week!</p></li><li><p>A publicly available detailed <a href="https://doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1" target="_blank" rel="noreferrer">experimental protocol</a>.</p></li></ul><p>We already have scientists from several different research groups scheduled to visit our lab in the coming months to learn the assay; please reach out if you are interested in trying it yourself!</p><h2 id="what-s-next" tabindex="-1">What&#39;s next? <a class="header-anchor" href="#what-s-next" aria-label="Permalink to &quot;What&#39;s next?&quot;">​</a></h2><p>Our lab has already extended this assay to measure ~10,000 neutralization titers of human sera against recent H3N2 strains, and we are hopeful these data can eventually be used to understand which influenza strains are evolutionarily successful, thereby helping with vaccine-strain selection. Stay tuned for more on this soon!</p><p>Also, feel free to reach out if you are interested in using the large sets of neutralization titers for evolutionarily or epidemiological modeling. All the raw data from the study described above is <a href="https://github.com/jbloomlab/flu_seqneut_pdmH1N1_2023-2024" target="_blank" rel="noreferrer">publicly available</a>; we&#39;re also happy to share interim data from our in-progress studies that we haven&#39;t yet pre-printed or published.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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-    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><h1>Deep mutational scanning of H5 influenza hemagglutinin</h1><!--[--><div style="position:relative;"><div><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p><hr><h2 id="overview" tabindex="-1">Overview <a class="header-anchor" href="#overview" aria-label="Permalink to &quot;Overview&quot;">​</a></h2><p>H5 influenza from clade 2.3.4.4b <a href="https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article" target="_blank" rel="noreferrer">has been causing</a> outbreaks in numerous animals, including wild birds, poultry, cats, and cattle. There is concern that this virus could pose a potential risk to humans if it acquires additional mutations that improve its ability to infect or transmit in humans. From prior work, several molecular phenotypes of HA are known to contribute to pandemic risk.</p><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study led by Bernadeta Dadonaite</a>, we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.</p><p><img src="/assets/research/h5-dms/phenotypes.jpg" alt="molecular phenotypes measured"></p><p>To make these measurements safely, we used a previously described <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus deep mutational scanning system</a> that allows us to characterize the effects of mutations to viral entry proteins using single-cycle replicative lentiviral particles that can be safely studied at biosafety-level 2. Using this system, we made libraries that covered all amino-acid mutations to the current candidate vaccine strain HA for clade 2.3.4.4b H5 influenza.</p><p><img src="/assets/research/h5-dms/schematic.jpg" alt="pseudovirus schematic"></p><p>First we measured how all mutations affected the ability of HA to mediate cell entry. These results can be visualized either using a heatmap or by projecting functional constraint onto the HA protein structure, as show below. Overall, these measurements identify functionally constrained regions of HA that are unlikely to mutate, and so form good targets for antibodies and other therapeutics.</p><p><img src="/assets/research/h5-dms/cell_entry_heatmap.jpg" alt="cell entry heatmap"><img src="/assets/research/h5-dms/cell_entry_structure.jpg" alt="cell entry structure"></p><p>Next we measured how mutations affect HA&#39;s ability to mediate entry into 293T cells that express a2-6 versus a2-3 linked sialic acids, which is important because human transmissible viruses use a2-6. Below are mutations that increase a2-6 usage:</p><p><img src="/assets/research/h5-dms/a2-6.jpg" alt="a2-6 usage"></p><p>We also measured how mutations affect HA stability, which is important as increased HA stability is associated with increased airborne transmissibility. Below is a map of stability enhancing mutations, which tend to be located in helices in the fusion machinery and interfaces between the head and stalk domains:</p><p><img src="/assets/research/h5-dms/stability.jpg" alt="stability"></p><p>Finally, we measured how all the mutations affect neutralization by mouse and ferret sera. The key sites of neutralization escape are on the top of the HA head mostly in classically defined antigenic regions, although sites of escape differ a bit between mouse and ferret sera:</p><p><img src="/assets/research/h5-dms/escape.jpg" alt="escape"></p><p>To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see <a href="https://nextstrain.org/groups/moncla-lab/h5nx/h5-dms/clade-2344b" target="_blank" rel="noreferrer">here</a> to color a phylogenetic tree by the measured phenotypes).</p><p>Angie Hinrichs <a href="https://x.com/AngieSHinrichs/status/1804270714570313873" target="_blank" rel="noreferrer">has also integrated the data into the UShER H5 trees</a>.</p><h2 id="how-to-visualize-and-access-the-data" tabindex="-1">How to visualize and access the data <a class="header-anchor" href="#how-to-visualize-and-access-the-data" aria-label="Permalink to &quot;How to visualize and access the data&quot;">​</a></h2><p>To make the data as accessible as possible for use by others, see</p><ul><li><p>An <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">interactive page</a> that allows you to visually examine heatmaps showing the effects of all the mutations on each measured phenotype.</p></li><li><p>An <a href="https://dms-viz.github.io/v0/?data=https%3A%2F%2Fraw.githubusercontent.com%2Fdms-vep%2FFlu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS%2Fmain%2Fresults%2Fdms-viz%2Fdms-viz.json" target="_blank" rel="noreferrer">interactive structure-based visualization</a></p></li><li><p>The <a href="https://github.com/dms-vep/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/blob/main/results/summaries/phenotypes.csv" target="_blank" rel="noreferrer">numerical values of the measurements</a> available.</p></li><li><p>Note that there are multiple HA numbering schemes in use, so make sure <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/numbering.html" target="_blank" rel="noreferrer">you understand how the mutations are being numbered</a>.</p></li></ul><h2 id="see-also" tabindex="-1">See also <a class="header-anchor" href="#see-also" aria-label="Permalink to &quot;See also&quot;">​</a></h2><p>See also <a href="https://x.com/jbloom_lab/status/1794364494858346803" target="_blank" rel="noreferrer">Jesse&#39;s Twitter thread</a> and <a href="https://slides.com/jbloom/h5-dms-short" target="_blank" rel="noreferrer">some slides about the study</a>.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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-    <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="divide-y divide-gray-200"><div class="pt-6 pb-8 space-y-2 md:space-y-5"><h1 class="text-3xl leading-9 font-bold text-gray-800 tracking-tight sm:text-4xl sm:leading-10 md:text-6xl md:leading-14"> Bloom Lab Blog </h1><p class="text-lg leading-7 text-gray-600"> A collection of thoughts, ideas, and projects from the Bloom Lab team. </p></div><ul class="divide-y divide-gray-200"><!--[--><li class="py-12"><article class="space-y-2 xl:grid xl:grid-cols-4 xl:space-y-0 xl:items-baseline"><dl><dt class="sr-only">Published on</dt><dd class="text-base leading-6 font-medium text-gray-500"><time datetime="May 25, 2024">May 25, 2024</time></dd></dl><div class="space-y-5 xl:col-span-3"><div class="space-y-6"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 no-underline" href="/posts/h5-dms.html">Deep mutational scanning of H5 influenza hemagglutinin</a></h2><div class="max-w-none text-gray-500"><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk.
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+</div></div><div class="text-base leading-6 font-medium"><a class="text-custom-orange no-underline" aria-label="read more about {{ post.title }}" href="/posts/2024-09-24_flu_seqneut.html">Read more →</a></div></div></article></li><li class="py-12"><article class="space-y-2 xl:grid xl:grid-cols-4 xl:space-y-0 xl:items-baseline"><dl><dt class="sr-only">Published on</dt><dd class="text-base leading-6 font-medium text-gray-500"><time datetime="May 25, 2024">May 25, 2024</time></dd></dl><div class="space-y-5 xl:col-span-3"><div class="space-y-6"><h2 class="text-2xl leading-8 font-bold tracking-tight"><a class="text-gray-900 hover:text-gray-900 no-underline" href="/posts/2024-05-25_h5-dms.html">Deep mutational scanning of H5 influenza hemagglutinin</a></h2><div class="max-w-none text-gray-500"><p>In <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">a new study</a>, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk.
 The data can be interactively visualized at <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/</a></p>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><!--[--><div style="position:relative;"><div><p>Snakemake pipeline for analyzing deep mutational scanning of barcoded viral entry proteins.</p><hr></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><!--[--><div style="position:relative;"><div><p>Interactive web tool for visualizing mutation data on a protein structure.</p><hr></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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 </div><p class="max-w-none text-gray-700 mt-2 md:mt-4"> Check out the <a href="https://jbloomlab.github.io/neutcurve" rel="external" target="_blank">documentation</a></p></div></div><div class="flex flex-col md:flex-row items-center"><div><div class="w-full border-t border-gray-200 block md:hidden mb-5"></div><h3 class="text-2xl leading-8 font-bold tracking-tight"><code class="bg-gray-200"><a href="https://jbloomlab.github.io/polyclonal/" rel="external" target="_blank" class="no-underline">polyclonal</a></code></h3><div class="max-w-none text-gray-500 mt-2"><p>Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.</p>
 </div><p class="max-w-none text-gray-700 mt-2 md:mt-4"> Check out the <a href="https://jbloomlab.github.io/polyclonal/" rel="external" target="_blank">documentation</a></p></div></div><div class="flex flex-col md:flex-row items-center"><div><div class="w-full border-t border-gray-200 block md:hidden mb-5"></div><h3 class="text-2xl leading-8 font-bold tracking-tight"><code class="bg-gray-200"><a href="https://github.com/jbloomlab/seqneut-pipeline" rel="external" target="_blank" class="no-underline">seqneut-pipeline</a></code></h3><div class="max-w-none text-gray-500 mt-2"><p>Snakemake pipeline for analyzing sequencing-based neutralization assays.</p>
 </div><p class="max-w-none text-gray-700 mt-2 md:mt-4"> Check out the <a href="https://github.com/jbloomlab/seqneut-pipeline" rel="external" target="_blank">documentation</a></p></div></div><!--]--></div></div><!--]--></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><!--[--><div style="position:relative;"><div><p>Python package for modeling mutational escape from polyclonal antibodies using deep mutational scanning data.</p><hr></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><!--[--><div style="position:relative;"><div><p>Snakemake pipeline for analyzing sequencing-based neutralization assays.</p><hr></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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@@ -36,7 +36,7 @@ <h2 id="big-datasets-and-viral-evolution" tabindex="-1">Big Datasets and Viral E
 <p>We have also integrated thousands of deep mutational scanning measurements into an <a href="https://jbloomlab.github.io/SARS2-RBD-escape-calc/" target="_blank" rel="noreferrer">antibody-escape calculator</a> that was <a href="https://slides.com/jbloom/sars2-rbd-escape-calc#/12" target="_blank" rel="noreferrer">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p>
 <p>We also have projects that involve analyzing the evolution of viruses <a href="https://elifesciences.org/articles/26875" target="_blank" rel="noreferrer">within individual infected humans</a>, and developing models to <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank" rel="noreferrer">understand epistasis among viral mutations</a>.</p>
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     <div id="app"><div id="app" class="flex flex-col min-h-screen"><nav class="p-4 mb-4"><div class="flex justify-between items-center w-full px-4 select-none"><a href="/" class="flex items-center no-underline"><img src="/images/icon.png" alt="Logo" class="h-8 w-8 mr-2"><span class="title text-lg font-bold text-custom-orange collapse sm:visible">Bloom Lab</span></a><button class="flex md:hidden text-gray-600"><span class="i-menu h-6 w-6"></span></button><div class="flex bg-custom-soft backdrop-blur-md md:backdrop-blur-none flex-col md:flex-row bg-opacity-75 md:bg-transparent md:flex md:items-center md:px-0 px-3 md:pb-0 pb-10 md:static absolute md:w-auto w-full md:h-auto h-full md:pt-0 pt-10 top-14 z-50 md:flex hidden left-[-100%]"><!--[--><a href="/research/" class="text-custom-orange text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Research</a><a href="/posts/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Blog</a><a href="/papers/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Papers</a><a href="/people/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Team</a><a href="/projects/" class="text-gray-600 text-xl md:text-lg px-4 py-4 md:py-2 flex items-center justify-center md:flex-none md:items-stretch md:justify-start" data-v-1c4acd03>Software</a><!--]--></div></div></nav><main class="flex-1 max-w-3xl mx-auto px-4 sm:px-6 lg:max-w-5xl xl:px-0"><div class="prose max-w-none"><h1>Our Research</h1><!--[--><div style="position:relative;"><div><h2 id="deep-mutational-scanning" tabindex="-1">Deep Mutational Scanning <a class="header-anchor" href="#deep-mutational-scanning" aria-label="Permalink to &quot;Deep Mutational Scanning&quot;">​</a></h2><p>Our lab uses deep mutational scanning to experimentally measure how tens-of-thousands of mutations to viral proteins affect key properties including function, immune escape, and receptor binding.</p><p><img src="/assets/research/dms.png" alt="&quot;Pseudovirus neutralization system&quot;"></p><p>We primarily perform these experiments using a <a href="https://www.sciencedirect.com/science/article/pii/S0092867423001034" target="_blank" rel="noreferrer">pseudovirus system</a> that allows us to safely characterize mutants of entry proteins from a wide range of viruses, including <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">SARS-CoV-2 spike</a>, <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">influenza hemagglutinin</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1074761324003194" target="_blank" rel="noreferrer">Lassa virus GPC</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1931312823002184" target="_blank" rel="noreferrer">HIV envelope</a>, and <a href="https://doi.org/10.1101/2024.04.17.589977" target="_blank" rel="noreferrer">Nipah virus RBP</a>.</p><p>Deep mutational scanning can inform efforts to <a href="https://www.nature.com/articles/s41586-024-07636-1" target="_blank" rel="noreferrer">forecast the evolution of human seasonal viruses</a> and <a href="https://doi.org/10.1101/2024.05.23.595634" target="_blank" rel="noreferrer">surveil the evolution of potential pandemic viruses</a>. To facilitate the use of deep mutational scanning for these important goals, we develop <a href="https://dms-viz.github.io/" target="_blank" rel="noreferrer">interactive visualization tools</a> and <a href="https://github.com/dms-vep/dms-vep-pipeline-3" target="_blank" rel="noreferrer">data analysis pipelines</a>. See <a href="https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/" target="_blank" rel="noreferrer">here</a> for an example of how we analyze and visualize large datasets to inform the study of viral evolution.</p><h2 id="interplay-of-immunity-and-viral-evolution" tabindex="-1">Interplay of Immunity and Viral Evolution <a class="header-anchor" href="#interplay-of-immunity-and-viral-evolution" aria-label="Permalink to &quot;Interplay of Immunity and Viral Evolution&quot;">​</a></h2><p>We study immunity and viral evolution at both the population and single-cell levels.</p><p><img src="/assets/research/seqneut.jpg" alt="&quot;Sequencing-based neutralization assay&quot;"></p><p>At the population level, differences in exposure history and immune imprinting lead human individuals to make antibody responses that target different regions of rapidly evolving viruses like influenza and SARS-CoV-2. This population heterogeneity has profound implications for viral evolution and disease susceptibility, as it causes viral mutations to impact the immunity of different individuals differently. We are characterizing this population heterogeneity using both <a href="https://www.sciencedirect.com/science/article/pii/S1931312824002336" target="_blank" rel="noreferrer">deep mutational scanning</a> and a <a href="https://doi.org/10.1101/2024.03.08.584176" target="_blank" rel="noreferrer">sequencing based-neutralization assay</a> we developed that increases the throughput of traditional neutralization assays by several orders of magnitude (see schematic at left).</p><p>At the single-cell level, we developed approaches to <a href="https://journals.asm.org/doi/10.1128/jvi.00500-19" target="_blank" rel="noreferrer">sequence viruses in single cells</a> and <a href="https://elifesciences.org/articles/86852" target="_blank" rel="noreferrer">quantify how many progeny each infected cell produces</a>. We use these approaches to understand how viral variation impacts the outcome of infection in individual cells.</p><h2 id="big-datasets-and-viral-evolution" tabindex="-1">Big Datasets and Viral Evolution <a class="header-anchor" href="#big-datasets-and-viral-evolution" aria-label="Permalink to &quot;Big Datasets and Viral Evolution&quot;">​</a></h2><p>We also develop new ways to leverage large datasets to better understand viral evolution.</p><p>We have come up with a way to leverage the millions of publicly available SARS-CoV-2 sequences to estimate the effect of individual mutations on viral fitness (see <a href="https://academic.oup.com/ve/article/9/2/vead055/7265011" target="_blank" rel="noreferrer">this paper</a> and <a href="https://slides.com/jbloom/sars2-mut-fitness/" target="_blank" rel="noreferrer">these slides</a>). We&#39;ve also created a platform to <a href="https://jbloomlab.github.io/SARS2-mut-fitness/" target="_blank" rel="noreferrer">visualize the mutational effects</a> to aid in interpretation of viral evolution.</p><p>We have also integrated thousands of deep mutational scanning measurements into an <a href="https://jbloomlab.github.io/SARS2-RBD-escape-calc/" target="_blank" rel="noreferrer">antibody-escape calculator</a> that was <a href="https://slides.com/jbloom/sars2-rbd-escape-calc#/12" target="_blank" rel="noreferrer">widely used</a> during the SARS-CoV-2 pandemic to understand the antigenic effects of viral mutations.</p><p>We also have projects that involve analyzing the evolution of viruses <a href="https://elifesciences.org/articles/26875" target="_blank" rel="noreferrer">within individual infected humans</a>, and developing models to <a href="https://academic.oup.com/ve/article/8/2/veac110/6889254" target="_blank" rel="noreferrer">understand epistasis among viral mutations</a>.</p></div></div><!--]--></div></main><footer class="w-full p-4 bg-white text-center text-gray-400 text-sm"><p> Copyright © Jesse Bloom 2024-Present </p></footer></div></div>
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