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 <!DOCTYPE html>
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 <h1>Introduction to the SARS-CoV-2 Genome Browser</h1>
  <div class="row">
   <div class="col-sm-6">
 <p>
 The UCSC Genome Browser is an open-source, interactive sequence visualization tool that 
 has been a cornerstone of genomics since we released the first human genome assembly 
 20 years ago. Cited in more than 37,000 scientific articles and used by thousands of 
 researchers each day; it allows for cross-referencing of research, clinical, 
 and epidemiology data against reference genomes, including 
 <a href="../../cgi-bin/hgGateway?db=wuhCor1">SARS-CoV-2</a>. This data is continuously 
 updated and added to as new datasets become available. For a more thorough description,
 please reference our <a href="https://www.nature.com/articles/s41588-020-0700-8" target="_blank">
 SARS-CoV-2 Genome Browser Nature Genetics paper</a>. We also post updates and COVID Browser
 resources to out <a href="../../covid19.html">COVID-19 Browser home page</a>.</p>
 <p>
 This guide will go through some of the most important use cases of the SARS-CoV-2 Genome Browser. 
 These topics include:</p>
 <ul>
 <li><a href="#nav">Orientation and Navigation</a></li>
 <li><a href="#genes">Gene Data and Sequence Alignments</a></li>
 <li><a href="#var">Variation and Immunology data</a></li>
 <li><a href="#usher">Phylogenetic Contact Tracing using USHER</a></li>
 <li><a href="#data">Other tools and data downloads</a></li>
 <li><a href="#support">Support and Collaboration</a></li>
 </ul>
 <p>
 For those who prefer a video explanation, we also have the following tutorial:</p>
  </div>
  <div class="col-md-6">
 <p>
   <iframe width="560" height="315" src="https://www.youtube.com/embed/Ee6h0xyZDOM?rel=0" 
   frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" 
   allowfullscreen></iframe></p>
  </div>
 </div>
 
 
 <a name="nav"></a>
 <h2>Genome Browser Orientation and Navigation</h2>
 <p>
 The standardized reference genome displayed on the 
-<a href=../../hgTracks?db=wuhCor1">COVID Genome Browser</a> is from one of the first isolated 
+<a href="../../cgi-bin/hgTracks?db=wuhCor1">COVID Genome Browser</a> is from one of the first isolated
 cases, known as <a href="https://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2" 
 target="_blank">NC_045512v2</a> or wuhCor1. With more than 80 track datasets across the 
 SARS-CoV-2 reference genome's nearly 30,000 RNA
 bases, navigation is essential to finding the information you want to see. Below is an example
 view of the SARS-CoV-2 Genome Browser with labeled sections highlighting the navigation, 
 reference sequence, annotations, and other available track datasets.</p>
 
 <p>
 <b>Navigation controls</b> at the top allow users to move left and right and to zoom. 
 The <b>search box</b> allows users to search for particular features or to move 
 to exact genomic coordinates. The <b>RNA sequence</b> is shown at the top only when the view 
 is sufficiently zoomed in. Annotations are shown for data tracks that have been set to 
 visible in the <b>available tracks</b> section at the bottom.
 Tracks can be configured with a right-click or by clicking on their name near the 
 bottom of the page.</p>
 
 <p class="text-center">
   <a href="http://genome.ucsc.edu/s/SARS_CoV2/Figure1"><img class="text-center" 
     src="../../images/covidBrowserIntroNav.png" 
     alt="Labeled orientation to the Genome Browser" width="1200" height="594"></a>
   <p class="gbsCaption text-center">This is a view of the SARS-CoV-2 Genome Browser (COVID Browser)
     with labeled elements to help with orientation. Interact with this session by clicking on 
     the picture. To read the full caption, please go to our 
     <a href="https://www.nature.com/articles/s41588-020-0700-8#Fig1" target="_blank">
     Nature Genetics paper</a>.
   </p>
 </p>
 
 <a name="genes"></a>
 <h2>Genes and Sequence Alignments</h2>
 <div class="row">
   <div class="col-md-5">
 <p>
 Gene and protein annotations are organized by the contributor, most notably NCBI and UniProt. 
 Having multiple information sources allows a consensus to be formed among datasets.
 Like many viral genomes, molecular complexity arises from polyproteins rearranging, 
 generating ~29 protein products. Most notable among these is the S (spike) protein which defines
 coronaviruses and allows entry into cell membrane. Additional tracks contain information such 
 as interactions between viral proteins and human proteins (protein interact), PDB structures, and 
 RNA structure annotations (Rangan RNA), and more.</p> 
 
 <p>
 Sequence alignments and conservation data are also available across the SARS-CoV-2 genome,
 from large-scale views to individual bases and amino acids. Four conservation
 tracks compare sequences with 44 bat coronaviruses, 119 vertebrate 
 coronaviruses, 7 human coronaviruses, and PhyloCSF computed conservation scores. 
 The tracks display differently depending on visibility mode and the number of 
 bases on the screen.</p>
 
 <p>
 Datasets can be turned on by setting the dropdown 
 next to the data track name from &quot;hide&quot; to dense, squish, pack, or full. Then click 
 the <button>refresh</button> button to see these changes in effect.
 Clicking on a data track name will take you to a description with more information on the 
 dataset, display conventions, methods, and references. Clicking on a particular item 
 will take you to a page with complete information about that item and dataset.</p>
   </div>
 
 
   <div class="col-md-7">
 <p class="text-center">
   <a href="http://genome.ucsc.edu/s/dschmelt/covidBrowserIntroGenes"><img class="text-center" 
     src="../../images/covidBrowserIntroGenes.png" 
     alt="Some of the gene and conservation data on the Genome Browser" width="700" height="375"></a>
   <p class="gbsCaption text-center">This Genome Browser display shows some of the gene and 
     conservation tracks available on the SARS-CoV-2 genome. You should be able to see UniProt 
     protein products, regions of interest, and domains all mapped against the SARS-CoV-2 genome.
     Below those tracks are two different conservation alignments in &quot;squish&quot; and 
     &quot;pack&quot; formats, comparing bat-host and human-host coronavirus sequences with the 
     reference SARS-CoV-2 genome. Interact with this session by clicking on the picture. 
   </p>
 </p>
  </div>
 </div>
 
 <a name="var"></a>
 <h2>Exploring Variation and Immunology Data</h2>
 <div class="row">
   <div class="col-md-5">
 <p>
 The <a href="../../cgi-bin/hgTracks?db=wuhCor1">SARS-CoV-2 Genome Browser</a> displays data on variation within SARS-CoV-2
 from UniProt, GenBank, GISAID, Nexstrain, and other providers. These datasets cover global trends
 in SARS-CoV-2 variation among all available public sequences, with regional descriptions 
 available through clicking into a particular entry. A few of the most notable tracks under the
 &quot;Variation and Repeats&quot; section are the 
 <a href="../../cgi-bin/hgTrackUi?db=wuhCor1&g=sarsCov2PhyloPub">Phylogeny: Public track</a>, which shows a 
 continuously updating phylogenetic tree that clusters similar sequences, with the frequency of each
 mutation shown by the height of the bar at that particular base. Tools are provided to filter these 
 data to show only well-supported mutation calls, set thresholds for minor-allele frequency, and display 
 data for specific clades.</p>
 <p>
 Another track is the 
 spike protein mutations from community annotations, highlighted as amino acid changes with red
 indicating strong antibody escape in receptor-binding domain (RBD) mutation screens. The Genome 
 Browser has also has the 
 <a href="../../cgi-bin/hgTrackUi?db=wuhCor1&g=variantMuts">Variants of Concern track</a>, which 
 pinpoints each accumulated mutation that defines 4 strains of SARS-CoV-2 
 of particular concern, labeled based on lay terms (such as 'California variant') as well as 
 the using the lineage defined by the 
 <a href="https://github.com/cov-lineages/pangolin/" target="_blank">Pangolin software</a> 
 (such as 'B.1.1.7').</p>
 
 <p>
 The Genome Browser also provides 12 immunology datasets that can inform potential therapeutic 
 targets or public health risks. Protein epitopes are highlighted in the genome by multiple tracks, 
 including those from the <a href="https://www.iedb.org/" target="_blank">
 Immune Epitope Database (IEDB)</a> and from 
 <a href="../../cgi-bin/hgTrackUi?db=wuhCor1&g=targets">a study of COVID+ patients</a>.
 Of particular interest are the datasets describing surveys of antibody response across 
 a variety of SARS-CoV-2 variants in the receptor-binding domain 
 (<a href="../../cgi-bin/hgTrackUi?db=wuhCor1&g=abEscape">Antibody Escape Mutations</a>).</p>
   </div>
 
   <div class="col-md-7">
 <p class="text-center">
   <a href="http://genome.ucsc.edu/s/dschmelt/covidBrowserIntroVars"><img class="text-center" 
     src="../../images/covidBrowserIntroVars.png" 
     alt="Some of the variation and immunology data on the Genome Browser" width="800" height="427"></a>
   <p class="gbsCaption text-center">This image shows some of the variation data tracks
   that can be displayed on the SARS-CoV-2 genome, specifically zoomed into the receptor-binding domain of 
   the Spike protein. Validated epitopes are displayed in black that may be a target for 
   therapeutic antibodies. In red and black, antibody escape scores are are shown for each 
   genome position. Smaller tick marks show amino acid or nucleotide changes from different sources,
   with more information available by clicking into the item.</p>
 </p>
 </div>
 </div>
 <a name="usher"></a>
 <h2>Genetic Contact Tracing with UShER</h2>
 <p>
 The UCSC Genome Browser has developed a tool that allows placement of SARS-CoV-2
 sequences onto existing phylogenetic trees far faster than previous methods, allowing 
 instantaneous tracing of strains and transmission events. This tool is called 
 <a href="../../cgi-bin/hgPhyloPlace">Ultrafast Sample placement on Existing tRees (UShER)</a> and
 exists as an interactive web-tool to compare sequences and link to existing public phylogenetic 
 trees.
 <p class="text-center">
   <a href="../../cgi-bin/hgPhyloPlace"><img class="text-center" 
     src="../../images/covidBrowserIntroUShER.png" 
     alt="Example of the UShER phylogeny placement tool" width="1200" 
     height="355"></a>
   <p class="gbsCaption text-center">After uploading a Fasta file, the tool returns a page with quality 
 metrics such as: number of bases aligned, number of Ns, and number of maximally parsimonious 
 placements along with the lineage and clade of the nearest neighbor. Colored boxes highlight 
 possible quality issues, green meaning this was a high confidence placement.</p>
 
 <h3>SARS-CoV-2/ COVID Phylogenic Trees</h3>
 <p>
 You can view your aligned SARS-CoV-2 sequence genotypes along with their closest known 
 relatives among the 150,000+ public sequences. You can compare among your uploaded 
 samples or trace possible transmission vectors using mutational signatures.</p>
 
 <p class="text-center">
   <a href="http://genome.ucsc.edu/s/dschmelt/covidBrowserIntroUShER2"><img class="text-center" 
     src="../../images/covidBrowserIntroUShER2.png" 
     alt="Example of the UShER phylogeny placement tool tree features" width="800" 
     height="427"></a>
   <p class="gbsCaption text-center">The uploaded sequences are highlighted in blue alongside 
 their most closely aligned public sequences. You can investigate genotypes and relationships 
 between samples.</p>
 </p>
 
 
 <a name="data"></a>
 <h2>Other tools, downloads, and features</h2>
 <h3>Custom Tracks, BLAT, Track Hubs</h3>
 <p>
 Along with a suite of data tracks, filters, and visualization options for the SARS-CoV-2
 genome, the UCSC Genome Browser offers many additional ways to interface with our data. 
 You can upload your data on the reference genome in 
 <a href="../../FAQ/FAQformat.html">nearly any format</a> with our
 <a href="../../cgi-bin/hgCustom">Custom Track tool</a>. If you have unaligned sequence,
  you can use our <a href="../../cgi-bin/hgBlat">BLAT
 sequence alignment tool</a> to get coordinates and base-by-base comparison 
 with any reference genome. We also display formatted data
 as <a href="hgTrackHubHelp.html">Track Hubs</a> and curate a list of 
 user-submitted <a href="../../cgi-bin/hgHubConnect?#publicHubs">Public Track Hubs</a>.
 </p>
 <h3>Downloads, Table Browser, JSON API, SQL</h3>
 <p>
 As part of our open-source, open-access philosophy, we try to make it as easy as possible 
 for researchers to download entire datasets or filtered subsets. Each track description page
 has a Data Access section which points users to our main options for data download.
 For downloading complete datasets, our 
 <a href="http://hgdownload.soe.ucsc.edu/downloads.html#SARS-CoV-2">SARS-CoV-2 download 
 directory</a> provides access to all our source files for transparency and reproducibility. 
 Our <a href="../../cgi-bin/hgTables">Table Browser</a> tool lets users interact with our
 data using a variety of filters based on score, identifiers, or any other field. Table Browser
 also allows users to convert data into multiple different formats (e.g. BED, GTF) and to access
 different formatted sequence outputs (in FASTA format).</p>
 
 <p>
 We have a <a href="api.html">JSON API</a> which can be programmatically called and return
 any dataset in its entirety or as a filtered subset based on documented input parameter. We also
 offer a <a href="mysql.html">Public SQL server</a> for similar flexible, automatic way to access
 genomic data and annotations. Along with this particular virus genome browser, we have thousands of
 genomes available for visualization and analysis from our <a href="../../cgi-bin/hgGateway">
 genome assemblies</a> gateway page.
 </p>
 
 <a name="support"></a>
 <h2>Support and Collaboration</h2>
 <p>
 The Genome Browser offers rapid email support for anything related to our tools. If your 
 question is general or may have been asked before, please review our 
 <a href="hgTracksHelp.html">Browser documentation</a> and our archive 
 of <a href="https://groups.google.com/u/1/a/soe.ucsc.edu/g/genome">
 previously answered questions</a>. If you would still like help, please go to
 our <a href="../../contacts.html">Contact Us</a> page to see access our email support. When contacting us, 
 please include a session link, images, and example data if applicable. We are active on 
 social media, you can follow us on <a href="https://twitter.com/GenomeBrowser">Twitter</a>
 or <a href="https://www.facebook.com/ucscGenomeBrowser">Facebook</a>.</p>
 
 <p>
 We are always looking to collaborate with researchers and add new datasets to our site. 
 We also seek to continuously improve our tools to meet the needs of the scientific community. 
 If you have any collaboration ideas, contributions, or feature requests, please reach out through
 our <a href="../../cgi-bin/hgUserSuggestion">suggestion page</a>.</p>
 
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