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 <h2>Description</h2>
 
 <p> This track collection shows <a href="https://sites.google.com/site/revelgenomics/"
 target="_blank">Rare Exome Variant Ensemble Learner</a> (REVEL) scores for predicting
 the deleteriousness of each nucleotide change in the genome.
 </p>
 
 <p>
 REVEL is an ensemble method for predicting the pathogenicity of missense variants 
 based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, 
 VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, 
 SiPhy, phyloP, and phastCons.  REVEL was trained using recently discovered pathogenic 
 and rare neutral missense variants, excluding those previously used to train its 
 constituent tools.  The REVEL score for an individual missense variant can range 
 from 0 to 1, with higher scores reflecting greater likelihood that the variant is 
 disease-causing. 
 </p>
 
 <h2>Display Conventions and Configuration</h2>
 <p>
 There are four subtracks for this track: one for every nucleotide showing
 a score for the mutation represented by a mutation from the reference to that
 nucleotide. All subtracks show the REVEL ensemble score on mouseover, representing
 each of the possible &#126;9 billion SNVs in the genome. The score is an aggregation 
 of the outputs of the 13 tools.  
 </p>
 
 <p>
 For single nucleotide variants (SNV), at every
 genome position, there are three values per position, one for every possible
 nucleotide mutation. The fourth value, &quot;no mutation&quot;, representing 
 the reference allele, e.g. A to A, is always set to zero, "0.0". REVEL only 
 takes into account amino acid changes, so a nucleotide change that results in no
 amino acid change (synonymous) also receives the score "0.0".
-<br>
+</p>
+<p>
 When using this track, zoom in until you can see every basepair at the
 top of the display. Otherwise, there are several nucleotides per pixel under 
 your mouse cursor and no score will be shown on the mouseover tooltip.
 </p>
 
 <p>For hg38, note that the data was converted from the hg19 data using the UCSC
 liftOver program, by the REVEL authors. This can lead to missing values or
 duplicated values. When a hg38 position is annotated with two scores due to the
 lifting, the authors removed all the scores for this position. They did the same when
 the reference allele has changed from hg19 to hg38.  Also, on hg38, the track has
 the "lifted" icon to indicate
 this. You can double-check if a nucleotide
 position is possibly affected by the lifting procedure by activating the track
 "Hg19 Mapping" under "Mapping and Sequencing".
 </p>
 
 <h2>Data access</h2>
 <p>
 REVEL scores are available at the 
 <a href="https://sites.google.com/site/revelgenomics/" target="_blank">
 REVEL website</a>.  
 The site provides precomputed REVEL scores for all possible human missense variants 
 to facilitate the identification of pathogenic variants among the large number of 
 rare variants discovered in sequencing studies.
 
 </p>
 
 <p>
 The REVEL data on the UCSC Genome Browser can be explored interactively with the
 <a href="../cgi-bin/hgTables">Table Browser</a> or the
 <a href="../cgi-bin/hgIntegrator">Data Integrator</a>.
 For automated download and analysis, the genome annotation is stored at UCSC in bigWig
 files that can be downloaded from
 <a href="http://hgdownload.soe.ucsc.edu/gbdb/$db/revel/" target="_blank">our download server</a>.
 The files for this track are called <tt>a.bw, c.bw, g.bw, t.bw</tt>. Individual
 regions or the whole genome annotation can be obtained using our tool <tt>bigWigToWig</tt>
 which can be compiled from the source code or downloaded as a precompiled
 binary for your system. Instructions for downloading source code and binaries can be found
 <a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads">here</a>.
 The tools can also be used to obtain features confined to given range, e.g.
 <br>&nbsp;
 <br>
 <tt>bigWigToBedGraph -chrom=chr1 -start=100000 -end=100500 http://hgdownload.soe.ucsc.edu/gbdb/$db/revel/a.bw stdout</tt>
 <br>
 
 <h2>Methods</h2>
 
 <p>
 Data were converted from the files provided on
 <a href="https://sites.google.com/site/revelgenomics/downloads?authuser=0" 
 target = "_blank">the REVEL Downloads website</a>. As with all other tracks,
 a full log of all commands used for the conversion is available in our 
 <a target=_blank href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/">source repository</a>, for <a target=_blank href="https://raw.githubusercontent.com/ucscGenomeBrowser/kent/master/src/hg/makeDb/doc/hg19.txt">hg19</a> and <a target=_blank href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/revel.txt">hg38</a>. The release used for each assembly is shown on the track description page.
 
 </p>
 
 <h2>Credits</h2>
 <p>
 Thanks to the REVEL development team for providing precomputed data and fixing duplicated values in the hg38 files.
 </p>
 
 <h2>References</h2>
 <p>
 Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, 
 Musolf A, Li Q, Holzinger E, Karyadi D, et al.
 <a href="https://doi.org/10.1016/j.ajhg.2016.08.016" target = _blank">
 REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants</a>
 <em>Am J Hum Genet</em>. 2016 Oct 6;99(4):877-885.
 PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/27666373" target="_blank">27666373</a>;
 PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065685/" target="_blank">PMC5065685</a>
 </p>