46a13fea0463e7ab3d3fe0f131476abbb7eca421 max Thu Sep 2 02:14:44 2021 -0700 Extending REVEL track docs after ML ticket, refs #28087 diff --git src/hg/makeDb/trackDb/human/revel.html src/hg/makeDb/trackDb/human/revel.html index 3e5f21a..c32209b 100644 --- src/hg/makeDb/trackDb/human/revel.html +++ src/hg/makeDb/trackDb/human/revel.html @@ -4,30 +4,41 @@ 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> +<p>Most authors of deleteriousness scores argue against using fixed cutoffs in +diagnostics. But to give an idea of the meaning of the score value, the REVEL +authors note: "For example, 75.4% of disease mutations but only 10.9% of +neutral variants (and 12.4% of all ESVs) have a REVEL score above 0.5, +corresponding to a sensitivity of 0.754 and specificity of 0.891. Selecting a +more stringent REVEL score threshold of 0.75 would result in higher specificity +but lower sensitivity, with 52.1% of disease mutations, 3.3% of neutral +variants, and 4.1% of all ESVs being classified as pathogenic". (Figure S1 of +the reference below) +</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 ~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, "no mutation", 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