GPS-Project-Website/project_outline.html at master · StephanieWLo/GPS-Project-Website · GitHub

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<!DOCTYPE html>
<html lang="en">

<head>
  <meta http-equiv="Content-Type" content="text/html; charset=UTF-8">
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  <title>GPS :: Global Pneumococcal Sequencing Project</title>
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        <div class="logo">
          <h1><i class=""></i><a href="index.html"><span class="color">GPS</span></a></h1>
          <div class="hmeta">Global Pneumococcal Sequencing Project</div>
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              <li class=""><a id="summary" href="project_outline.html">Project Outline</a></li>
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              <li class=""><a id="resources_overview" href="resources_overview.html">Overview</a></li>
              <li class=""><a id="sampling_map" href="sampling_map.html">Countries</a></li>
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          <h1><i class="fa fa-pencil-square-o blue"></i> Project Outline</h1>
        </header>
        <div class="row desc">
          <div class="col-lg-9 col-md-9">
            <h2>Pneumococcal Disease</h2>

            <p><i>Streptococcus pneumoniae</i> (the pneumococcus) is the leading vaccine preventable cause of pneumonia,
              septicaemia and meningitis in young children. In 2015, it was estimated to be responsible for about 9
              million cases of disease and over 317,000 deaths in children under 5 with the main burden in low- and
              middle- income countries (<a target="_blank"
                href="https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(18)30247-X/fulltext">Wahl
                2018</a>).</p>


            <img src="img/streptococcus.png" />


            <p>Pneumococcal conjugate vaccines (PCVs) target the capsule surrounding pneumococcal cells has proven to be
              very effective in reducing pneumococcal disease since its advent in 2000. However, there are at least <a
                target="_blank" href="serotypes.html">100 different forms of capsule</a>, or serotypes, based on
              antigen-antibody reaction. The current PCVs are only able to target some serotypes and the population
              overall is able to evolve to evade the vaccine. This creates an arms race between vaccine and
              pneumococcus.</p>

            <h2>GPS</h2>

            <p>The Global Pneumococcal Sequencing (GPS) project, established in 2011, was set out to create a global
              picture of the pneumococcal evolution during the vaccine introductions using whole-genome sequencing. The
              information has enabled us to better understand how the pneumococcus makes its capsule and makes its
              escape, and improve the design of new vaccines.</p>
            <p>By the end of 2019, the GPS project sequenced >26,000 pneumococcal isolates from >50 countries,
              representing a global collaboration of almost 100 scientists from around the world. Like previous studies,
              we have seen that after the introduction of vaccines, pneumococci with vaccine serotypes were replaced by
              those with non-vaccine serotypes. But with large-scale genome data, we have gone beyond that, looking for
              the first time at all the strains circulating globally.</p>
            <p>The GPS project has made a major breakthrough in defining pneumococcal strains in high-resolution by
              taking genome-wide DNA variations into account (<a target="_blank"
                href="https://www.thelancet.com/article/S2352-3964(19)30259-2/fulltext">Gladstone and Lo et al
                2019</a>). This robust typing method is coupled with a coherent and dynamic naming system (<a
                target="_blank" href="GPSC_lineages.html">GPSC</a>) so as to enable joint efforts in tracking
              pneumococcal lineages across geographical regions and over time, especially before and after the roll-out
              of PCVs.</p>
            <p>Using this typing scheme, we found a subset of strains were globally disseminated, many of which were
              associated with antibiotic resistance and composed of vaccine- and non-vaccine serotypes. Our recent work,
              published in the <i>Lancet Infectious Diseases</i>, has shown that these globally-spreading strains played
              an important role in the arms race by driving the expansion of pneumococcal bacteria with non-vaccine
              targets (<a target="_blank"
                href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30297-X/fulltext">Lo and
                Gladstone et al 2019</a>).</p>
            <p>The DNA data also allowed us to unlock the genetic diversity of the capsule and discovered nine potential
              new serotypes (<a target="_blank"
                href="https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000274">van Tonder et al
                2019</a>) and shed light on previously unrecognised antimicrobial resistance in pneumococcus (<a
                target="_blank" href="https://academic.oup.com/jac/article/75/3/512/5650366">Lo et al 2019</a>). For
              more exciting findings, please browse our <a target="_blank" href="publications.html">publication
                page</a>.</p>

            <h2>Open data and findings</h2>

            <p>The GPS project generates a rich source of genome and epidemiological data for tracking pneumococcal
              transmission and evolution on both national and international levels. The genome data are deposited in <a
                target="_blank" href="https://www.ebi.ac.uk/ena/data/view/PRJEB3084">ENA</a>. High-level analyses are
              interactively presented by <a target="_blank" href="sampling_map.html">countries</a> and by <a
                target="_blank" href="GPSC_lineages.html">strains</a> using <a target="_blank"
                href="https://microreact.org/">Microreact</a> and <a target="_blank"
                href="https://jameshadfield.github.io/phandango/#/GPS">Phandango</a>. Illustrations of how to use these
              resources are summarised in a recent publication (<a target="_blank"
                href="https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.000357?originator=authorOffprint&identity=176964&timestamp=20210430151417&signature=3ebadc206d0b1fda9098a00fc65d31ec">Gladstone
                et al 2020</a>) and videos on the <a target="_blank" href="resources_overview.html">Resources pages</a>.
            </p>

            <h2>What’s next?</h2>

            <p>In 2020, the GPS project is marching into the next chapter, GPS2. The outputs of GPS highlight the needs
              on
            <ol>
              <li><strong>Increasing geographical coverage</strong> in countries with high disease burden, such as
                India, Nigeria, DRC Congo and Pakistan, together these four countries accounted for approximately 50% of
                global pneumococcal disease burden in 2015.</li>

              <li><strong>Supporting local data generation and analysis</strong> to achieve a working system for ongoing
                genomic surveillance in LMICs by providing capacity building and <a target="_blank"
                  href="https://training.bactgen.sanger.ac.uk/">bioinformatics training</a>.</li>

              <li><strong>Engaging with policy makers</strong> to communicate the value of the data and the importance
                of study findings for decision-making in pneumococcal disease prevention.</li>
            </ol>

            The success of the GPS project has also opened up opportunities to establish strategic partnership with
            <ol>
              <li><a target="_blank" href="https://redsirevanetwork.com/">SIREVA</a> to establish a framework for
                integrating whole-genome sequencing in the ongoing surveillance in Latin America.</li>

              <li><a target="_blank" href="https://www.uab.edu/medicine/immunology/faculty/136-mah-lab">Professor Moon
                  Nahm’s lab</a> at the University of Alabama to characterise capsule structure of the nine potential
                new serotypes.</li>
            </ol>

            Last but not least, we thank <a target="_blank" href="https://www.gatesfoundation.org/">the Bill & Melinda
              Gates Foundation</a> to fund this project.</p>


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          <div class="col-lg-3 col-md-3 other-links">
            <header>
              <i class="fa fa-external-link lblue"></i>
              Related Links
            </header>
            <p>
              <a href="https://sangerinstitute.blog/2019/06/12/tracking-a-deadly-shapeshifter" target="_blank">The story
                of GPS</a>
            </p>
            <p>
              <a href="https://www.sanger.ac.uk/news_item/pneumonia-mapped-largest-genomic-survey-any-disease-causing-bacterium/"
                target="_blank">GPS headline findings</a>
            </p>
            <p>
              <a href="https://view-hub.org/" target="_blank">View-hub reports, disease burden, vaccine access and
                coverage</a>
            </p>
            <p>
              <a href="https://www.gavi.org" target="_blank">Gavi, the Vaccine Alliance</a>
            </p>

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