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240 changes: 72 additions & 168 deletions .../2018-07-16-genomic-surveillance-idm.html → ...ts/2018-07-16-real-time-tracking-idm.html
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---
layout: talk_reveal3
title: Genomic surveillance of emerging threats and epidemic spread
title: Real-time tracking of virus evolution
venue: IDM
event: Weekly Seminar
author: Trevor Bedford
Expand All @@ -23,6 +23,8 @@ <h1 class="title">{{ page.title }}</h1>
{{ page.venue }}
</section>

<!------------------------------->

<section>
<h2>Sequencing to reconstruct pathogen spread</h2>
</section>
Expand All @@ -48,171 +50,16 @@ <h3>Sequence and determine phylogeny</h3>
</section>

<section>
<h2>Phylogenetic tracking critical to pandemic warning systems and outbreak response</h2>
</section>

<section style="text-align: left;">
<h3>Monitoring of animal-to-human spillover</h3>
<p>
&nbsp; &nbsp; &nbsp;
<i>MERS spillover in the Arabian Peninsula</i>
</p>
<br>
<h3>Monitoring of human-to-human transmission</h3>
<p>
&nbsp; &nbsp; &nbsp;
<i>Ebola spread in West Africa</i>
<br>
&nbsp; &nbsp; &nbsp;
<i>Zika spread in the Americas</i>
</p>
</section>

<section data-background="#000">
<h1 class="title">MERS-CoV</h1>
</section>

<section style="text-align: left;">
<h3>Middle East respiratory syndrome coronavirus (MERS-CoV)</h3>
<p>
<ul>
<li>First identified in Saudi Arabia in 2012</li>
<li>2220 confirmed cases to date and 790 deaths</li>
<li>Camels thought to be the intermediate host</li>
<li>30% of common colds due to endemic human coronaviruses</li>
</ul>
</p>
</section>

<section>
<h3>Ongoing incidence, but lack of epidemic growth</h3>
<img class="stretch" src="/images/talks/mers_who_timeseries.png">
</section>

<section>
<h3>Cases localized to the Arabian Peninsula</h3>
<img class="stretch" src="/images/talks/mers_map.jpg">
</section>

<section>
<h3>Hypotheses for MERS transmission</h3>
<img class="stretch" src="/images/talks/mers_network.png">
</section>

<section>
<h3>MERS-CoV spillover at the camel-human interface</h3>
<p class="smaller"><i>
with <img width=40 class="img-avatar" src="/images/team/gytis-dudas.jpg"> Gytis Dudas, Luiz Carvalho and Andrew Rambaut
</i></p>
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<section style="text-align: left;">
<h3>Genomic dataset</h3>
<p>
<ul>
<li>174 virus genomes from human infections</li>
<li>100 virus genomes from camel infections</li>
</ul>
</p>
</section>

<section>
<h3>MERS tree with host state</h3>
<img class="stretch" src="/images/talks/mers_tree_ml.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<section>
<h3>Phylodynamic reconstruction of host state</h3>
<img class="stretch" src="/images/talks/mers_tree.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<section>
<h3>Humans are transient hosts</h3>
<img class="stretch" src="/images/talks/mers_exploded_tree.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<!-- <section>
<h3>Asymmetric migration rates</h3>
<p>
<ul>
<li>56 (48–63) camel-to-human transmission events resulting in 174 sequenced human infections</li>
<li>3 (0-12) human-to-camel transmission events</li>
</ul>
</p>
<img class="stretch" src="/images/talks/mers_mig_rates.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section> -->
<!--
<section>
<h3>Introduction events tend to occur between April and July</h3>
<img class="stretch" src="/images/talks/mers_seasonality.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>
<section data-background="/images/talks/mers_camel_calving.jpg">
<h3 class="title">Dromedary camel calving occurs between Nov and Feb</h3>
<br><p><br><p><br><p><br><p><br><p><br><p><br><p><br><p><br><p><br><p><br><p><br><p>
</section> -->

<section>
<h3>Monte Carlo simulation</h3>
<img class="stretch" src="/images/talks/mers_abc_method.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<section>

<section>
<h3>Phylogenetic clustering suggests $R_0$ below 1.0 and ~2000 human cases driven by ~600 introduction events</h3>
<img class="stretch" src="/images/talks/mers_cluster_r0_combined.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

<section>
<h3>Similar results when we assume larger clusters are more likely to be sequenced</h3>
<img class="stretch" src="/images/talks/mers_cluster_r0_bias.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
</section>

</section>

<section>
<h3>Critically, no evidence of increasing cluster sizes through time</h3>
<img class="stretch" src="/images/talks/mers_introductions.png">
<div class="citation">
<a href="/papers/dudas-mers-structure/">Dudas et al. 2018. eLife.</a>
</div>
<h2>Phylogenetic tracking has the capacity to revolutionize epidemiology</h2>
</section>

<section style="text-align: left;">
<h3>Many other viruses that exhibit stuttering chains of human infection</h3>
<h3>Outline</h3>
<p>
<ul>
<li>Nipah virus (fruit bats / pigs, Southeast Asia)</li>
<li>Lassa virus (rodents, West Africa)</li>
<li>Avian influenza (birds, mainland China)</li>
<li>Ebola spread in West Africa</li>
<li>Zika spread in the Americas</li>
<li>"Real-time" analyses</li>
</ul>
</p>
</section>
Expand Down Expand Up @@ -242,13 +89,13 @@ <h3>Sequencing of 1610 Ebola virus genomes collected during the 2013-2016 West A
</div>
</section>

<!-- <section>
<section>
<h3>Sequenced genomes were representative of spatiotemporal diversity</h3>
<img class="stretch" data-src="/images/talks/ebola_mig_sampling_corr.png">
<div class="citation">
<a href="/papers/dudas-ebola-epidemic-spread/">Dudas et al. 2017. Nature.</a>
</div>
</section> -->
</section>

<section>
<h3>Phylogenetic reconstruction of epidemic</h3>
Expand All @@ -257,7 +104,7 @@ <h3>Phylogenetic reconstruction of epidemic</h3>
<a href="/papers/dudas-ebola-epidemic-spread/">Dudas et al. 2017. Nature.</a>
</div>
</section>
<!--

<section data-background="/images/talks/ebola_mig_tree.png">
</section>

Expand All @@ -283,7 +130,7 @@ <h3>Effect of borders on migration rates</h3>
<div class="citation">
<a href="/papers/dudas-ebola-epidemic-spread/">Dudas et al. 2017. Nature.</a>
</div>
</section> -->
</section>

<section>
<h3>Spatial structure at the country level</h3>
Expand Down Expand Up @@ -431,6 +278,34 @@ <h3>Nextstrain architecture</h3>
<img class="stretch" src="/images/talks/nextstrain_components.png">
</section>

<section style="text-align: left;">
<h2><a href="https://github.com/nextstrain/fauna">Fauna</a></h2>
<p>
<b>Rethink database of virus and titer data</b>
</p>
<p >
<ul>
<li>Harmonizes data from different sources</li>
<li>Integrates different types of data (serology, sequences, case details)</li>
<li>Provides an interface for downstream analysis</li>
<ul>
</p>
</section>

<section style="text-align: left;">
<h2><a href="https://github.com/nextstrain/augur">Augur</a></h2>
<p>
<b>Build scripts to align sequences, build trees and annotate</b>
</p>
<p>
<ul>
<li>Flexible build scripts to incorporate different viruses and analyses</li>
<li>Constructs time-resolved phylogenies</li>
<li>Annotates with geographic transitions and mutation events</li>
<ul>
</p>
</section>

<section style="text-align: left;">
<h3>Example augur pipeline for 1600 Ebola genomes</h3>
<p>
Expand All @@ -443,6 +318,37 @@ <h3>Example augur pipeline for 1600 Ebola genomes</h3>
</p>
</section>

<section>
<div class="left" style="float:left;width:63%">
<h3>Pipeline consists of Unix-like command line modules</h3>
<p>
<ul>
<li>Modules called via <code>augur filter</code>, <code>augur tree</code>, <code>augur traits</code>, etc...
<li>Designed to be composable across pathogen builds</li>
<li>Uses Snakemake to define a pipeline, making steps obvious</li>
<li>Provides depedency graph for fast recomputation</li>
<li>Pathogen-specific repos give users an obvious foundation to build off of</li>
</ul>
</div>
<div class="right" style="float:right;width:35%">
<img data-src="/images/talks/nextstrain_augur_dag.png">
</div>
</section>

<section style="text-align: left;">
<h2><a href="https://github.com/nextstrain/auspice">Auspice</a></h2>
<p>
<b>Web visualization of resulting trees</b>
</p>
<p>
<ul>
<li>Interactive data exploration and filtering</li>
<li>Framework through React / D3</li>
<li>Connects phylogeny, geography and genotypes</li>
<ul>
</p>
</section>

<section data-background="#000">
<h1 style="font-weight: 500;">
<a href="http://nextstrain.org/" target="_blank">
Expand Down Expand Up @@ -483,8 +389,6 @@ <h3>Acknowledgements</h3>
<img width=50 class="img-avatar" src="/images/team/thomas-sibley.jpg"> Tom Sibley
</p>

<p class="tiny"><b>MERS</b>: Gytis Dudas, Andrew Rambaut, Luiz Carvalho</p>

<p class="tiny"><b>Ebola</b>: Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Philippe Lemey,
Marc Suchard, Andrew Tatem</p>

Expand All @@ -493,7 +397,7 @@ <h3>Acknowledgements</h3>
Ester Sabino, Luiz Alcantara</p>

<p class="tiny"><b>Nextstrain</b>: Richard Neher, James Hadfield, Colin Megill, Sidney Bell,
Charlton Callender, Barney Potter, John Huddleston, Emma Hodcroft</p>
Charlton Callender, Barney Potter, John Huddleston, Emma Hodcroft, Tom Sibley</p>

<div class="pull-right" style="vertical-align: bottom; display: table-cell;">
<img width="15%" data-src="/images/talks/logo_fred_hutch_vertical.png">
Expand Down

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