3a884d87e2f5198d79e8c628fad94112ed4d1a01 max Mon Feb 15 05:48:31 2021 -0800 updating CADD track docs, refs #18492 diff --git src/hg/makeDb/trackDb/human/caddSuper.html src/hg/makeDb/trackDb/human/caddSuper.html new file mode 100644 index 0000000..68802e1 --- /dev/null +++ src/hg/makeDb/trackDb/human/caddSuper.html @@ -0,0 +1,110 @@ +<h2>Description</h2> + +<p> This track collection shows <a href="https://cadd.gs.washington.edu/" +target="_blank">Combined Annotation Dependent Depletion</a> scores. +CADD is a tool for scoring the deleteriousness of single nucleotide variants as +well as insertion/deletions variants in the human genome.</p> + +<p> +Some mutation annotations +tend to exploit a single information type (e.g. phastCons or phylP for +conservation) and/or are restricted in scope (e.g. to missense changes). Thus, +a broadly applicable metric that objectively weights and integrates diverse +information is needed. Combined Annotation Dependent Depletion (CADD) is a +framework that integrates multiple annotations into one metric by contrasting +variants that survived natural selection with simulated mutations. +</p> + +<p> +CADD scores strongly correlate with allelic diversity, pathogenicity of both +coding and non-coding variants, and experimentally measured regulatory effects, +and also highly rank causal variants within individual genome sequences. +Finally, CADD scores of complex trait-associated variants from genome-wide +association studies (GWAS) are significantly higher than matched controls and +correlate with study sample size, likely reflecting the increased accuracy of +larger GWAS. +</p> + +<h2>Display Conventions and Configuration</h2> +<p> +There are six subtracks of this track: four for every possible single nucleotide mutation, +one for insertions and one for deletions. All subtracks show the CADD Phred +score on mouse over.<p> + +<p> +<b>Single nucleotide variants (SNV):</b> For SNVs, at every +genome position, there are three values per position, one for every possible +nucleotide mutation. The fourth value, "no mutation", e.g. A to A, is always +set to zero.<br> +When using this track, please zoom in until you can see every basepair at the +top of the display. Otherwise, there are several nucleotides under your mouse +cursor per pixel and instead of an actual score, the tooltip text can only show +the average score of all nucleotides under the cursor, which is indicated by +the prefix "~" in the mouse over and averages of scores are not useful for any +application of CADD. +</p> + +<p><b>Insertions and deletions:</b>: Scores are also shown on mouse over for a +set of insertions and deletions. On hg38, the set has been obtained from +Gnomad3. On hg19, the set of indels has been obtained from various sources +(gnomAD2, ExAC, 1000 Genomes, ESP). If your insertion or deleletion of interest +is not in the track, you will need to use CADD's +<a target=_blank href="https://cadd.gs.washington.edu/score">Online scoring tool</a> +to obtain them.</p> + +<H2>Data access</H2> +<p> +CADD scores are freely available for all non-commercial applications from <a target=_blank href="https://cadd.gs.washington.edu/download">the CADD website</a>. For commercial applications, see <a target=_blank href="https://cadd.gs.washington.edu/contact">the license instructions</a> there. +</p> + +<p> +The CADD 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 and bigBed files that +can be downloaded from +<a href="http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/" target="_blank">our download server</a>. +The files for this track are called <tt>a.bw, c.bw, g.bw, t.bw, ins.bb and del.bb</tt>. Individual +regions or the whole genome annotation can be obtained using our tool <tt>bigWigToWig</tt> +or <tt>bigBedToBed</tt> which can be compiled from the source code or downloaded as a precompiled +binary for your system. Instructions for downloading source code and binaries can be found +<a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads">here</a>. +The tools +can also be used to obtain only features within a given range, e.g. <br> +<tt>bigWigToBedGraph -chrom=chr1 -start=100000 -end=100500 http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/a.bw stdout</tt><br> +or<br> +<tt>bigBedToBed -chrom=chr1 -start=100000 -end=100500 http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/ins.bb stdout</tt></p> + +<h2>Methods</h2> + +<p> +Data were converted from the files provided on +<a href="https://cadd.gs.washington.edu/download" target="_blank">the CADD Downloads website</a>, provided by the Kircher lab, +using <a href="https://github.com/ucscGenomeBrowser/kent/tree/master/src/hg/makeDb/cadd" target=_BLANK>custom Python scripts</a>, +documented in our <a target=_BLANK href="https://github.com/ucscGenomeBrowser/kent/blob/master/src/hg/makeDb/doc/hg38/cadd.txt">makeDoc</a> files. +</p> + +<h2>Credits</h2> +<p> +Thanks to the CADD development team for providing precomputed data as simple tab-separated files. +</p> + +<h2>References</h2> +<p> +Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. +<a href="http://dx.doi.org/10.1038/ng.2892" target="_blank"> + A general framework for estimating the relative pathogenicity of human genetic variants</a>. +<em>Nat Genet</em>. 2014 Mar;46(3):310-5. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/24487276" target="_blank">24487276</a>; PMC: <a + href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992975/" target="_blank">PMC3992975</a> +</p> + +<p> +Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. +<a href="https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gky1016" target="_blank"> + CADD: predicting the deleteriousness of variants throughout the human genome</a>. +<em>Nucleic Acids Res</em>. 2019 Jan 8;47(D1):D886-D894. +PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/30371827" target="_blank">30371827</a>; PMC: <a + href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323892/" target="_blank">PMC6323892</a> +</p> +