Merge pull request #22 from jbloomlab/update-blog

update blog
jbloomlab · Aug 5, 2024 · 926703d · 926703d
2 parents b3d8b8e + 3a770a8
commit 926703d
Show file tree

Hide file tree

Showing 10 changed files with 68 additions and 119 deletions.
diff --git a/assets/research/h5-dms/a2-6.jpg b/assets/research/h5-dms/a2-6.jpg
diff --git a/assets/research/h5-dms/cell_entry_heatmap.jpg b/assets/research/h5-dms/cell_entry_heatmap.jpg
diff --git a/assets/research/h5-dms/cell_entry_structure.jpg b/assets/research/h5-dms/cell_entry_structure.jpg
diff --git a/assets/research/h5-dms/escape.jpg b/assets/research/h5-dms/escape.jpg
diff --git a/assets/research/h5-dms/phenotypes.jpg b/assets/research/h5-dms/phenotypes.jpg
diff --git a/assets/research/h5-dms/schematic.jpg b/assets/research/h5-dms/schematic.jpg
diff --git a/assets/research/h5-dms/stability.jpg b/assets/research/h5-dms/stability.jpg
diff --git a/posts/add-post.md b/posts/add-post.md
diff --git a/posts/example-markdown.md b/posts/example-markdown.md
diff --git a/posts/h5-dms.md b/posts/h5-dms.md
@@ -0,0 +1,68 @@
+---
+layout: post
+title: Deep mutational scanning of H5 influenza hemagglutinin
+date: 2024-05-25
+author: Jesse Bloom
+---
+
+In [a new study](https://doi.org/10.1101/2024.05.23.595634), 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 [https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/](https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/)
+
+---
+
+## Overview
+
+H5 influenza from clade 2.3.4.4b [has been causing](https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article) 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.
+
+In [a new study led by Bernadeta Dadonaite](https://doi.org/10.1101/2024.05.23.595634), we used deep mutational scanning to measure how all HA amino-acid mutations affected key molecular phenotypes.
+
+![molecular phenotypes measured](../assets/research/h5-dms/phenotypes.jpg)
+
+To make these measurements safely, we used a previously described [pseudovirus deep mutational scanning system](https://www.sciencedirect.com/science/article/pii/S0092867423001034) 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.
+
+![pseudovirus schematic](../assets/research/h5-dms/schematic.jpg)
+
+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.
+
+![cell entry heatmap](../assets/research/h5-dms/cell_entry_heatmap.jpg)
+![cell entry structure](../assets/research/h5-dms/cell_entry_structure.jpg)
+
+Next we measured how mutations affect HA'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:
+
+![a2-6 usage](../assets/research/h5-dms/a2-6.jpg)
+
+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:
+
+![stability](../assets/research/h5-dms/stability.jpg)
+
+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:
+
+![escape](../assets/research/h5-dms/escape.jpg)
+
+To aid in using these data in surveillance, our collaborators (Jordan Ort and Louise Moncla) have integrated them into nextstrain (see [here](https://nextstrain.org/groups/moncla-lab/h5nx/h5-dms/clade-2344b) to color a phylogenetic tree by the measured phenotypes).
+
+Angie Hinrichs [has also integrated the data into the UShER H5 trees](https://x.com/AngieSHinrichs/status/1804270714570313873).
+
+## How to visualize and access the data
+To make the data as accessible as possible for use by others, see
+
+- An [interactive page](https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/) that allows you to visually examine heatmaps showing the effects of all the mutations on each measured phenotype.
+
+- An [interactive structure-based visualization](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)
+
+- The [numerical values of the measurements](https://github.com/dms-vep/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/blob/main/results/summaries/phenotypes.csv) available.
+
+- Note that there are multiple HA numbering schemes in use, so make sure [you understand how the mutations are being numbered](https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/numbering.html).
+
+## See also
+
+See also [Jesse's Twitter thread](https://x.com/jbloom_lab/status/1794364494858346803) and [some slides about the study](https://slides.com/jbloom/h5-dms-short).
+