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<!DOCTYPE html>
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<title>GPS :: Global Pneumococcal Sequencing Project</title>
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<h1><i class=""></i><a href="index.html"><span class="color">GPS</span></a></h1>
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<h1><i class="fa fa-pencil-square-o blue"></i> Sub-studies</h1>
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<p>Many sub-studies have developed from the GPS project and some of them have already been published in
high-quality journals and they are listed in the <a target="_blank" href="publications.html">publication</a>
page. Here is a list of on-going sub-studies:</p>
<!-- start substudies -->
<blockquote>
<h3>
Investigation of impact of vaccine on evolution of pneumococcal surface protein A (PspA) and its effect on pneumococcal virulence: a global perspective
</h3>
<strong>Shaper Mirza, Stephanie Lo, and Stephen Bentley</strong>
<br>
<em>Lahore University of Management Sciences and Wellcome Sanger Institute</em>
<p>
PspA is a choline binding protein and is known to be constitutively expressed throughout the life cycle of bacteria. This study will investigate the genetic diversity and evolution of pspA, improving our understanding of its potential as a vaccine target.
</p>
</blockquote>
<blockquote>
<h3>
Molecular characterisation and genomic epidemiology determination of invasive pneumococcal serotype 8 in South Africa using whole-genome sequencing analysis (2005 - 2020)
</h3>
<strong>Cebile Lekhuleni, Mignon du Plessis, Kedibone Ndlangisa, and Anne von Gottberg</strong>
<br>
<em>The National Institute For Communicable Diseases, South Africa</em>
<p>
Serotype 8 is an emerging serotype after the introduction of PCV13. This study will investigate the pneumococcal lineage driving the increase in serotype 8 in South Africa, and place it in the global context.
</p>
</blockquote>
<blockquote>
<h3>
Genetic diversity, serotype prediction and resistotyping of nasopharyngeal isolates of <em>S. pneumoniae</em> from Indian Hajj pilgrims by whole genome sequencing
</h3>
<strong>Geetha Nagaraj</strong>
<br>
<em>Kempegowda Institute of Medical Sciences, India</em>
<p>
The Islamic Hajj pilgrimage is the largest annual mass gathering in the world. This study will use whole-genome sequencing to understand transmission dynamics during the Indian Hajj pilgrims.
</p>
</blockquote>
<blockquote>
<h3>A Retrospective Study of invasive <em>Streptococcus pneumoniae</em> serotype 2 infections causing
meningitis in Bangladesh and Africa</h3>
<strong>Samir Saha</strong>
<br>
<em>The Child Health Research Foundation</em>
<p>Serotype 2 is currently the most common cause of meningitis in Bangladesh though it is rare elsewhere.
This study aims to understand the pathogenicity of meningitis-causing serotype 2 pneumococci in Bangladesh
using comparative genomics.</p>
</blockquote>
<blockquote>
<h3>Comparing pneumococcal population structure to understand patterns of local strain prevalence and the
impact of geographic transmission</h3>
<strong>Rama Kandasamy, Rebecca Gladstone, Nicholas Croucher, Andrew J. Pollard, Stephen Bentley</strong>
<br>
<em>University of Oxford</em>
<p>Studies consistently demonstrate geographical differences in pneumococcal serotype-specific distribution.
This study aims to identify the dynamics of novel strains and transmission events between regions.</p>
</blockquote>
<blockquote>
<h3>Defining the mechanisms and evolution of cotrimoxazole resistance in a global dataset of
<i>Streptococcus pneumoniae</i></h3>
<strong>Jennifer Cornick, Anmol Kiran, Dean Everett</strong>
<br>
<em>Malawi-Liverpool-Wellcome Trust Clinical Research Programme</em>
<p>The relatively low concordance in cotrimoxazole susceptibility between phenotype and genotype highlights
our knowledge gap in understanding its resistance mechanisms. This study aims to improve our understanding
on this topic using GWAS analysis.</p>
</blockquote>
<blockquote>
<h3>Detect relative contributions of mutation and gene exchange within the major circulating clones</h3>
<strong>Stephen Bentley, Rebecca Gladstone</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>It is known that there is a subset of pneumococcal strains or clones that are globally disseminated. This
study will make clear how mutation and genetic exchange contribute to the success of a strain.</p>
</blockquote>
<blockquote>
<h3>Detect transmission of successful pneumococcal clones on an international scale</h3>
<strong>Stephen Bentley, Rebecca Gladstone</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>There are a handful of successful pneumococcal strains and this study is set out to understand the
phylodynamic of predominant pneumococcal clones.</p>
</blockquote>
<blockquote>
<h3>Determination of the genes at the CPS locus and correlation with the backbone genotype</h3>
<strong>Stephen Bentley, Rebecca Gladstone</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>Serology allows us to type pneumococci into different serotypes. Using genome data, we will look beyond
the genes encoding capsule and characterise its relation to the rest of the genome.</p>
</blockquote>
<blockquote>
<h3>Determine the patterns and mechanisms of antibiotic resistance acquisition in a number of developing
countries</h3>
<strong>Stephen Bentley, Rebecca Gladstone</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>In many LMICs, antibiotic-selective pressure is strong. Understanding the mechanisms of how pneumococci
acquire antibiotic resistance will shed light on development of cutting-edge intervention measures.</p>
</blockquote>
<blockquote>
<h3>Diversity of ribosomal mutations associated with MLS resistance</h3>
<strong>Paulina Hawkins</strong>
<br>
<em>Centers for Disease Control and Prevention</em>
<p>Macrolide has increasingly been used as empirical treatment for respiratory tract infection. After PCV13,
rising macrolide resistance was observed in pneumococci with non-vaccine serotype (<a target="_blank"
href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30297-X/fulltext">Lo et al
2019</a>). This study will improve our understanding of the genetic diversity of ribosomal mutations
related to macrolide resistance in <em>S. pneumoniae</em>.</p>
</blockquote>
<blockquote>
<h3>Emergence of a cotrimoxazole resistant serotype 16F lineage GPSC46 in an intensively vaccinated African
birth cohort</h3>
<strong>Felix Dube, Stephanie Lo</strong>
<br>
<em>Wellcome Sanger Institute and University of Cape Town</em>
<p>In a longitudinal carriage study in Drakenstein, serotype 16F appears to be a common serotype and most of
them belong to GPSC46. This study combines the GPSC46 isolates from both studies to understand its global
distribution and evolution.</p>
</blockquote>
<blockquote>
<h3>Epidemiology of invasive pneumococcal disease in Thailand, 2009-2012</h3>
<strong>Rebecca Hocknell, David W. Cleary, Somporn Srifeungfung, Stuart Clarke</strong>
<br>
<em>University of Southampton and Siam University</em>
<p>Current understanding of invasive pneumococcal disease in Thailand is very limited, and this sub-study
will probably be the first to report the population structure of IPD isolates in this region and served as
the baseline data to evaluate the PCV impact once it is implemented nationally.</p>
</blockquote>
<blockquote>
<h3>Evolution of CC63 (PMEN25) pre and post PCV introduction</h3>
<strong>Paulina Hawkins</strong>
<br>
<em>Centers for Disease Control and Prevention</em>
<p>CC63 belongs to GPSC9 is one of the top globally-spreading strain after PCV13. It is multidrug-resistant.
This study will shed light on adaptation and evolution under vaccine-selective pressure.</p>
</blockquote>
<blockquote>
<h3>Genetic diversity and distribution of the pneumococcal ABC transporter proteins and implications on
potential protein-based vaccines.</h3>
<strong>Ebrima Bojang</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>Bacterial ABC transporter is a class of transmembrane transporters that are important for virulence. This
study will improve our understanding in their genetic diversity which will shed light on a conservative
target for potential vaccine development.</p>
</blockquote>
<blockquote>
<h3>Genomic insight into the evolution of <em>Streptococcus pneumoniae</em> CC63 in India</h3>
<strong>Balaji Veeraraghavan</strong>
<br>
<em>Christian Medical College</em>
<p>CC63 is one of the predominant pneumococcal clones in India and this study aims to understand the
evolution of CC63 in India during the vaccine introduction.</p>
</blockquote>
<blockquote>
<h3>Global distribution and evolution of major penicillin binding proteins that determine β-lactam
resistance in <em>Streptococcus pneumoniae</em></h3>
<strong>Yuan Li, Benjamin Metcalf, Lesley McGee, Bernard Beall, Stephen Bentley, Rebecca Gladstone</strong>
<br>
<em>Centers for Disease Control and Prevention</em>
<p><a target="_blank" href="https://www.cdc.gov/streplab/index.html">CDC Strep Lab</a> has a strong
expertise in using genomic data to predict antibiotic resistance in <em>S. pneumoniae</em>. This project
will appreciate the genetic diversity and evolution of the penicillin binding protein, that confer
resistance to the first-line antibiotic, β-lactam, in treating pneumococcal disease.</p>
</blockquote>
<blockquote>
<h3>Global distribution and evolution of <em>Streptococcus pneumoniae</em> GPSC3 (PMEN33)</h3>
<strong>Stephanie Lo</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>GPS headline paper on <a target="_blank"
href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30297-X/fulltext">Lancet
Infectious Diseases</a> has pointed out that GPSC3 is a major pneumococcal strain expressing non-vaccine
serotype after PCV13. Using a global collection, we will investigate the evolutionary history of this
important lineage and shed light on its secret of success.</p>
</blockquote>
<blockquote>
<h3>Global distribution and genomic diversity of serotype 5 in context of PCVs</h3>
<strong>Chrispin Chaguza, Rebecca Gladstone, Stephen Bentley</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>Serotype 5, as a vaccine target, is an invasive serotype that is included in PCV13. It is common in LMICs
in Sub Saharan Africa and Asia, but not developed countries. This study will improve our understanding of
the pneumococcal strains expressing serotype 5 and its changes during vaccine introduction.</p>
</blockquote>
<blockquote>
<h3>Global diversity of <em>Streptococcus pneumoniae</em> serotype 3 isolates; changes in the pre and post PCV eras
in comparison with the changes observed in a local collection set in Hong Kong</h3>
<strong>Pak-Leung Ho, Pierra Law</strong>
<br>
<em>University of Hong Kong</em>
<p><a target="_blank"
href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422485/pdf/khvi-15-02-1526555.pdf">Ho <em>et
al</em></a> has importantly reported that serotype 3 emerged after PCV13 in Hong Kong and its increase
was due to a regional-specific lineage that replaced the common serotype 3 clone CC180. This study will
elucidate the circulating serotype 3 strains in Hong Kong and understand this emerging strain’s
pathogenicity.</p>
</blockquote>
<blockquote>
<h3>Global emergence and population dynamics of <em>Streptococcus pneumoniae</em> serotype 19A/F CC320
(GPSC1)</h3>
<strong>Balaji Veeraraghavan</strong>
<br>
<em>Christian Medical College</em>
<p>GPSC1 is one of the major pneumococcal strains in India and this study will investigate its population
dynamics in India and place it in global context.</p>
</blockquote>
<blockquote>
<h3>Global population structure of serotype 12F pneumococci</h3>
<strong>Thi Minh Huynh, Kate Mellor, Stephanie Lo</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>
Emergence of serotype 12F after PCV13 was reported in multiple countries. This study will investigate the pneumococcal lineages driving the increase of 12F, and their antimicrobial resistance and transmission pattern.
</p>
</blockquote>
<blockquote>
<h3>Mitis streptococci in a disguise of <em>S. pneumoniae</em>: what is shared, what is distinct?</h3>
<strong>Ewa Sadowy</strong>
<br>
<em>National Medicines Institute</em>
<p><em>S. mitis</em> occasionally misidentified as <em>S. pneumoniae</em> in clinical laboratories. This
project will improve our understanding of the species boundaries using pan genome analysis.</p>
</blockquote>
<blockquote>
<h3>Modelling the pre/post vaccine distribution of accessory genome loci</h3>
<strong>Stephen Bentley, Nicholas Croucher</strong>
<br>
<em>Wellcome Sanger Institute and Imperial College London</em>
<p>Around 25% of each pneumococcal genome is composed of non-conserved, or ‘accessory’, genes. This study
will use a stochastic population model on them to understand why pneumococcal populations have their
observed structure, how they change following vaccination and what the effects of different vaccine
formulations would likely be, if introduced in different locations.</p>
</blockquote>
<blockquote>
<h3>Molecular Epidemiology of Pneumococcus Isolated from Invasive Pneumococcal Infection of Bangladeshi
Children</h3>
<strong>Roly Malaka, Stephanie Lo</strong>
<br>
<em>The Child Health Research Foundation and Wellcome Sanger Institute</em>
<p>Bangladesh introduced PCV10 in 2015. This study will report the population genetic structure, serotype
distribution and antimicrobial resistance of ~500 invasive pneumococcal disease isolates 2002-2015 and
serve as the baseline to evaluate the PCV impact in the future.</p>
</blockquote>
<blockquote>
<h3>Persistent colonisation of 19F in children from South Africa eight years after PCV7 introduction</h3>
<strong>Courtney Olwagen, Stephanie Lo</strong>
<br>
<em>University of Witwatersrand and Wellcome Sanger Institute</em>
<p>This study aims to elucidate why a vaccine targeted serotype has remained in the carriage population in
South Africa using bacterial GWAS.</p>
</blockquote>
<blockquote>
<h3>PneumoCaT2: an investigation into 19A-like cps from serotype 19F pneumococcal isolates</h3>
<strong>Carmen Sheppard, Stephanie Lo</strong>
<br>
<em>Public Health of England and Wellcome Sanger Institute</em>
<p>PHE developed a WGS-based tool<a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/27672516/">
PneumoCaT</a> to infer serotype from genome data. This study will harness the global collection in the
GPS project to understand a 19F divergent. The knowledge learned will ultimately be integrated into a new
version of PneumoCaT.</p>
</blockquote>
<blockquote>
<h3>Population genetic structure, serotype distribution and antibiotic resistance of <em>Streptococcus
pneumoniae</em> in Nigeria</h3>
<strong>Stephen Obaro, Stephanie Lo</strong>
<br>
<em>University of Nebraska Medical Center and Wellcome Sanger Institute</em>
<p>Nigeria introduced PCV10 in 2014. Current understanding about the epidemiology of <em>S. pneumoniae</em>
is scarce. This study will be the first to describe the pneumococcal population using whole-genome
sequencing during the introduction of PCV10.</p>
</blockquote>
<blockquote>
<h3>Population genomics of mobile genetic elements</h3>
<strong>Stephen Bentley and Nicholas Croucher</strong>
<br>
<em></em>
<p>Mobile genetic elements (MGEs) are common in pneumococcal genomes. This analysis will be focussed on
understanding how MGEs affect the diversification of pneumococci.</p>
</blockquote>
<blockquote>
<h3>Relationships and specific features of ST320/serotype 19A isolates from Poland</h3>
<strong>Ewa Sadowy</strong>
<br>
<em>National Medicines Institute</em>
<p>Multidrug resistant pneumococci of ST320, usually associated with 19A serotype are observed worldwide and
currently play an important role in invasive infections in Poland. This study will look into the Polish
ST320 isolates and place them in global context.</p>
</blockquote>
<blockquote>
<h3>Tracking the competitive evolutionary success of a pneumococcal lineage (PMEN15) as it adapts to
co-trimoxazole prophylaxis for HIV in South Africa</h3>
<strong>Stephanie Lo, Nicholas Croucher</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>South Africa is one of the countries with a high burden of HIV and co-trimoxazole was once introduced as
a prophylaxis for HIV patients. This study will investigate how this antibiotic-selective measure affects
the circulating pneumococcal lineage PMEN15.</p>
</blockquote>
<blockquote>
<h3>Using Machine Learning to predict cotrimoxazole resistance levels in <em>Streptococcus pneumoniae</em>
</h3>
<strong>Stephanie Lo and Nichole Wheeler</strong>
<br>
<em>Wellcome Sanger Institute</em>
<p>Cotrimoxazole resistance is achieved by stepwise mutations in <em>folA</em> and <em>folP</em> genes. The
current prediction based on known mutations highlights the needs for improvement. This study will develop
a machine learning model to predict cotrimoxazole MIC using genome sequences.</p>
</blockquote>
<blockquote>
<h3>Validation and improvement of predicting β-Lactam minimum inhibitory concentration of Streptococcus
pneumoniae using whole-genome sequencing and PBP typing</h3>
<strong>Yuan Li, Benjamin Metcalf, Lesley McGee, Bernard Beall, Mignon du Plessis, Anne von
Gottberg</strong>
<br>
<em>Centers for Disease Control and Prevention</em>
<p>The current machine learning model for prediction of β-Lactam MIC was built and validated using a
pneumococcal dataset from the USA (Li et al <a target="_blank"
href="https://mbio.asm.org/content/7/3/e00756-16">2016</a> and <a target="_blank"
href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558719/">2017</a>). This study will validate and
improve the prediction model using genome data from South Africa.</p>
</blockquote>
<!-- end substudies -->
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