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<li><a href="./">Pangenomics Workshop NCGR</a></li>
<li class="divider"></li>
<li class="chapter" data-level="1" data-path=""><a href="#introduction-to-pangenomics"><i class="fa fa-check"></i><b>1</b> Introduction to Pangenomics</a>
<ul>
<li class="chapter" data-level="1.1" data-path=""><a href="#what-is-a-pangenome"><i class="fa fa-check"></i><b>1.1</b> What is a “pangenome”?</a>
<ul>
<li class="chapter" data-level="1.1.1" data-path=""><a href="#open-vs.-closed-genomes"><i class="fa fa-check"></i><b>1.1.1</b> Open vs. Closed Genomes</a></li>
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<li class="chapter" data-level="1.1.3" data-path=""><a href="#pangenome-today"><i class="fa fa-check"></i><b>1.1.3</b> “Pangenome” Today</a></li>
<li class="chapter" data-level="1.1.4" data-path=""><a href="#the-benefit-of-pangenomes"><i class="fa fa-check"></i><b>1.1.4</b> The Benefit of Pangenomes</a></li>
<li class="chapter" data-level="1.1.5" data-path=""><a href="#what-are-pangenomes-good-for"><i class="fa fa-check"></i><b>1.1.5</b> What are pangenomes good for?</a></li>
<li class="chapter" data-level="1.1.6" data-path=""><a href="#computational-pangenomics"><i class="fa fa-check"></i><b>1.1.6</b> Computational Pangenomics</a></li>
<li class="chapter" data-level="1.1.7" data-path=""><a href="#pangenome-representations"><i class="fa fa-check"></i><b>1.1.7</b> Pangenome Representations</a></li>
<li class="chapter" data-level="1.1.8" data-path=""><a href="#genomevariation-graphs"><i class="fa fa-check"></i><b>1.1.8</b> Genome/Variation Graphs</a></li>
<li class="chapter" data-level="1.1.9" data-path=""><a href="#types-of-variation-graphs"><i class="fa fa-check"></i><b>1.1.9</b> Types of Variation Graphs</a></li>
<li class="chapter" data-level="1.1.10" data-path=""><a href="#mapping-reads-to-variation-graphs"><i class="fa fa-check"></i><b>1.1.10</b> Mapping Reads to Variation Graphs</a></li>
<li class="chapter" data-level="1.1.11" data-path=""><a href="#datayeast-genomes"><i class="fa fa-check"></i><b>1.1.11</b> Data/Yeast Genomes:</a></li>
<li class="chapter" data-level="1.1.12" data-path=""><a href="#yeast-assemblies"><i class="fa fa-check"></i><b>1.1.12</b> Yeast Assemblies</a></li>
<li class="chapter" data-level="1.1.13" data-path=""><a href="#sk1-illumina-reads"><i class="fa fa-check"></i><b>1.1.13</b> SK1 Illumina Reads</a></li>
<li class="chapter" data-level="1.1.14" data-path=""><a href="#cup1-gene"><i class="fa fa-check"></i><b>1.1.14</b> CUP1 Gene</a></li>
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<div id="introduction-to-pangenomics" class="section level1 hasAnchor" number="1">
<h1><span class="header-section-number">Chapter 1</span> Introduction to Pangenomics<a href="#introduction-to-pangenomics" class="anchor-section" aria-label="Anchor link to header"></a></h1>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/JoannAlan.png" style="width:65.0%" alt="" />
<p class="caption">Instructors</p>
</div>
<div id="what-is-a-pangenome" class="section level2 hasAnchor" number="1.1">
<h2><span class="header-section-number">1.1</span> What is a “pangenome”?<a href="#what-is-a-pangenome" class="anchor-section" aria-label="Anchor link to header"></a></h2>
<p>The term “pangenome” was first coined by Sigaux et al. and was used to describe a public database containing an assessment of genome and transcriptome alterations in major types of tumors, tissues, and experimental models.</p>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/Sigaux.png" style="width:65.0%" alt="" />
<p class="caption">Sigaux et al.</p>
</div>
<p>The term was later revitalized by Tettelin et al. to describe a microbial genome by which genes were in the core (present in all strains) and which genes were dispensable (missing from one or more of the strains).</p>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/Tettelin.png" style="width:65.0%" alt="" />
<p class="caption">Tettelin et al.</p>
</div>
<div id="open-vs.-closed-genomes" class="section level3 hasAnchor" number="1.1.1">
<h3><span class="header-section-number">1.1.1</span> Open vs. Closed Genomes<a href="#open-vs.-closed-genomes" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<p><img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/ClosedvOpen.png" style="width:65.0%" alt="Open and Closed Pangenomes" />
<a href="https://en.wikipedia.org/wiki/Pan-genome" class="uri">https://en.wikipedia.org/wiki/Pan-genome</a></p>
</div>
<div id="then-vs.-now" class="section level3 hasAnchor" number="1.1.2">
<h3><span class="header-section-number">1.1.2</span> Then vs. Now<a href="#then-vs.-now" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/CostGenome.png" style="width:90.0%" alt="" />
<p class="caption">Cost per Genome</p>
</div>
<p><a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data" class="uri">https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data</a></p>
<ul>
<li>Low Cost</li>
<li>High Quality Long Reads (HiFi)</li>
<li>Many reference-quality assemblies per species</li>
</ul>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/GenomePubs.png" style="width:75.0%" alt="" />
<p class="caption">Pangenome Publications</p>
</div>
<p><a href="https://www.nature.com/articles/s41477-020-0733-0" class="uri">https://www.nature.com/articles/s41477-020-0733-0</a></p>
</div>
<div id="pangenome-today" class="section level3 hasAnchor" number="1.1.3">
<h3><span class="header-section-number">1.1.3</span> “Pangenome” Today<a href="#pangenome-today" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<p>“Any collection of genomic sequences to be analyzed jointly or to be used as a reference. These sequences can be linked in a graph-like structure, or simply constitute sets of (aligned or unaligned) sequences.” – Computational Pangenomics Consortium</p>
</div>
<div id="the-benefit-of-pangenomes" class="section level3 hasAnchor" number="1.1.4">
<h3><span class="header-section-number">1.1.4</span> The Benefit of Pangenomes<a href="#the-benefit-of-pangenomes" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li>Removes reference bias</li>
</ol>
<ul>
<li>May only represent one organism</li>
<li>Could be a “mosaic”of individuals, i.e. doesn’t represent a coherent haplotype</li>
<li>Allele bias</li>
<li>Doesn’t include common variation</li>
</ul>
<ol start="2" style="list-style-type: decimal">
<li>Allow multiple assemblies to be analyzed simultaneously, i.e. efficiently</li>
</ol>
</div>
<div id="what-are-pangenomes-good-for" class="section level3 hasAnchor" number="1.1.5">
<h3><span class="header-section-number">1.1.5</span> What are pangenomes good for?<a href="#what-are-pangenomes-good-for" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li>Core vs dispensable genes:</li>
</ol>
<ul>
<li>How big is the core?</li>
<li>How big is the dispensable?</li>
<li>How big is the pangenome?</li>
<li>What traits are associated with the core/dispensable?</li>
</ul>
<ol start="2" style="list-style-type: decimal">
<li>Unbiased read mapping and variant calling</li>
<li>More robust variation-trait association</li>
<li>Visual exploration of genomic structure of population</li>
</ol>
</div>
<div id="computational-pangenomics" class="section level3 hasAnchor" number="1.1.6">
<h3><span class="header-section-number">1.1.6</span> Computational Pangenomics<a href="#computational-pangenomics" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<p>“Questions about efficient data structures, algorithms and statistical methods to perform bioinformatic analyses of pan-genomes give rise to the discipline of ‘computational pan-genomics’.”</p>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/Computational.png" style="width:90.0%" alt="" />
<p class="caption">Computational Pangenomics</p>
</div>
<p><a href="https://academic.oup.com/bib/article/19/1/118/2566735" class="uri">https://academic.oup.com/bib/article/19/1/118/2566735</a></p>
</div>
<div id="pangenome-representations" class="section level3 hasAnchor" number="1.1.7">
<h3><span class="header-section-number">1.1.7</span> Pangenome Representations<a href="#pangenome-representations" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li>Gene sets</li>
<li>Multiple sequence alignments</li>
<li>K-mer sets</li>
<li>Graphs</li>
</ol>
<ul>
<li>De Bruijn graphs</li>
<li>Haptotype graphs</li>
<li><strong>Genome/Variation graphs</strong></li>
</ul>
</div>
<div id="genomevariation-graphs" class="section level3 hasAnchor" number="1.1.8">
<h3><span class="header-section-number">1.1.8</span> Genome/Variation Graphs<a href="#genomevariation-graphs" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li><p>Variation forms bubbles Nodes represent sequences</p></li>
<li><p>Chains of nodes represent contiguous sequence in one or more assemblies</p></li>
<li><p>The sequences of nodes connected by an edge may overlap</p></li>
<li><p>Graphs can be acyclic or cyclic</p></li>
<li><p>Haplotypes are “threaded” through graph as paths</p></li>
</ol>
<p><img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/VariationGraphA.png" style="width:96.0%" alt="Pangenome Representations" />
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/VariationGraphB.png" style="width:96.0%" alt="Pangenome Representations" /></p>
<p><a href="https://academic.oup.com/bib/article/19/1/118/2566735" class="uri">https://academic.oup.com/bib/article/19/1/118/2566735</a></p>
</div>
<div id="types-of-variation-graphs" class="section level3 hasAnchor" number="1.1.9">
<h3><span class="header-section-number">1.1.9</span> Types of Variation Graphs<a href="#types-of-variation-graphs" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li>Reference Graph (vg)</li>
</ol>
<ul>
<li>A reference with variants</li>
<li>E.G. Human reference now includes VCF with common variation
<ul>
<li><a href="https://www.ncbi.nlm.nih.gov/genome/guide/human/" class="uri">https://www.ncbi.nlm.nih.gov/genome/guide/human/</a></li>
</ul></li>
</ul>
<ol start="2" style="list-style-type: decimal">
<li>Reference Backbone; “iterative” (minigraph)</li>
</ol>
<ul>
<li>Graph starts as reference and other sequences are layered
on, i.e. variants can be relative to sequences other than the
reference</li>
</ul>
<ol start="3" style="list-style-type: decimal">
<li>Reference-Free (cactus)</li>
</ol>
<ul>
<li>Graph is built using non-reference techniques, such as multiple sequence alignment</li>
</ul>
<p>These are all methods used by the Human <strong>Pangenome Reference Consortium</strong>
<a href="https://humanpangenome.org" class="uri">https://humanpangenome.org</a></p>
</div>
<div id="mapping-reads-to-variation-graphs" class="section level3 hasAnchor" number="1.1.10">
<h3><span class="header-section-number">1.1.10</span> Mapping Reads to Variation Graphs<a href="#mapping-reads-to-variation-graphs" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/ReadsToVariation.png" style="width:100.0%" alt="" />
<p class="caption">Genotyping Variation</p>
</div>
</div>
<div id="datayeast-genomes" class="section level3 hasAnchor" number="1.1.11">
<h3><span class="header-section-number">1.1.11</span> Data/Yeast Genomes:<a href="#datayeast-genomes" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/Yeast.png" style="width:100.0%" alt="" />
<p class="caption">Yeast Genomes</p>
</div>
<ol style="list-style-type: decimal">
<li>12 strains from Yeast Population Reference Panel (YPRP)</li>
</ol>
<ul>
<li><a href="https://yjx1217.github.io/Yeast_PacBio_2016/welcome/" class="uri">https://yjx1217.github.io/Yeast_PacBio_2016/welcome/</a></li>
<li>7 Saccharomyces cerevisiae (brewer’s yeast)
<ul>
<li>Includes S288C reference</li>
</ul></li>
<li>5 Saccharomyces paradoxus (wild yeast)</li>
</ul>
<ol start="2" style="list-style-type: decimal">
<li>Manuscript</li>
</ol>
<ul>
<li><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659681/" class="uri">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659681/</a></li>
</ul>
<ol start="3" style="list-style-type: decimal">
<li>Software (LRSDAY)</li>
</ol>
<ul>
<li>Manuscript
<ul>
<li><a href="https://www.nature.com/articles/nprot.2018.025" class="uri">https://www.nature.com/articles/nprot.2018.025</a></li>
</ul></li>
<li>GitHub
<ul>
<li><a href="https://github.com/yjx1217/LRSDAY" class="uri">https://github.com/yjx1217/LRSDAY</a>
<a href="https://link.springer.com/article/10.1186/s13059-020-1941-7" class="uri">https://link.springer.com/article/10.1186/s13059-020-1941-7</a></li>
</ul></li>
</ul>
</div>
<div id="yeast-assemblies" class="section level3 hasAnchor" number="1.1.12">
<h3><span class="header-section-number">1.1.12</span> Yeast Assemblies<a href="#yeast-assemblies" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<ol style="list-style-type: decimal">
<li>12 Mb</li>
<li>16 chromosomes</li>
<li>12 Yeast PacBio Assemblies (Chromosome level)</li>
</ol>
<ul>
<li>~100-200x PacBio sequencing reads</li>
<li>HGAP + Quiver polishing</li>
<li>~200-500x Illumina (Pilon correction)</li>
<li>Manual curation</li>
<li>Annotation</li>
</ul>
<ol start="4" style="list-style-type: decimal">
<li>Yeast Population Reference Panel (YPRP)</li>
</ol>
<ul>
<li><a href="https://yjx1217.github.io/Yeast_PacBio_2016/data/" class="uri">https://yjx1217.github.io/Yeast_PacBio_2016/data/</a></li>
</ul>
</div>
<div id="sk1-illumina-reads" class="section level3 hasAnchor" number="1.1.13">
<h3><span class="header-section-number">1.1.13</span> SK1 Illumina Reads<a href="#sk1-illumina-reads" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<p>SK1 is the most distant from S288C</p>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/YeastB.png" style="width:100.0%" alt="" />
<p class="caption">Yeast Genomes</p>
</div>
</div>
<div id="cup1-gene" class="section level3 hasAnchor" number="1.1.14">
<h3><span class="header-section-number">1.1.14</span> CUP1 Gene<a href="#cup1-gene" class="anchor-section" aria-label="Anchor link to header"></a></h3>
<div class="figure">
<img src="/Users/agomez/Desktop/Bookdown/Pangenomics/Figures/StructuralRearrangements.png" style="width:100.0%" alt="" />
<p class="caption">Structrual Rearrangements</p>
</div>
<ol style="list-style-type: decimal">
<li>CUP1</li>
</ol>
<ul>
<li>A gene involved in heavy metal (copper) tolerance with copy-number variation (CNV) in population.</li>
<li><a href="https://www.yeastgenome.org/locus/S000001095" class="uri">https://www.yeastgenome.org/locus/S000001095</a></li>
</ul>
<ol start="2" style="list-style-type: decimal">
<li>YHR054C</li>
</ol>
<ul>
<li>Putative protein of unknown function.</li>
<li><a href="https://www.yeastgenome.org/locus/S000001096" class="uri">https://www.yeastgenome.org/locus/S000001096</a></li>
</ul>
<p><a href="https://www.nature.com/articles/ng.3847" class="uri">https://www.nature.com/articles/ng.3847</a></p>
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