50d8ee9d40c249470a706bfa94dccfca19364707
max
  Tue Feb 9 09:07:22 2021 -0800
adding docs page for CADD track, refs #18492

diff --git src/hg/makeDb/trackDb/human/cadd.html src/hg/makeDb/trackDb/human/cadd.html
new file mode 100644
index 0000000..1717ca2
--- /dev/null
+++ src/hg/makeDb/trackDb/human/cadd.html
@@ -0,0 +1,98 @@
+<h2>Description</h2>
+
+<p> This track collection shows <a href="https://cadd.gs.washington.edu/"
+target="_blank">Combined Annotation Dependent Depletion</a> score.
+CADD is a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletions variants in the human genome.
+</p>
+
+<p>
+Many mutation annotations
+tend to exploit a single information type (e.g. 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>
+C-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, C-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 four 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>
+For single nucleotides, at every
+nucleotide position, with three values per position, one for every possible
+mutation. 
+For the single nucleotide variants, please zoom in until you can see every basepair. The mouse overs
+will other show averages over all nucleotides under the cursor, which is indicated by the prefix "~"
+in the mouse over text.
+</p>
+
+<p>The scores are also shown on mouse over for a set of insertions and deletions. On hg38, the selected
+set has been obtained from Gnomad3. On hg19, it has been obtained from XXX (TODO: ask CADD authors).
+</p>
+
+<H2>Data access</H2>
+<p>
+The raw data can be explored interactively with the <a href="../cgi-bin/hgTables">Table Browser</a>
+or the <a href="../cgi-bin/hgIntegrator">Data Integrator</a>.
+
+<p>
+For automated download and analysis, the genome annotation is stored in a bigWig file that
+can be downloaded from
+<a href="http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/" target="_blank">our download server</a>.
+The files for this track are called <tt>a.bw, c.bw, g.bw, t.bw, ins.bb and del.bb</tt>. Individual
+regions or the whole genome annotation can be obtained using our tool <tt>bigWigToWig</tt>
+which can be compiled from the source code or downloaded as a precompiled
+binary for your system. Instructions for downloading source code and binaries can be found
+<a href="http://hgdownload.soe.ucsc.edu/downloads.html#utilities_downloads">here</a>.
+The tool
+can also be used to obtain only features within a given range, e.g. 
+<tt>bigWigToBedGraph http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/a.bw stdout</tt></p>
+</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 Kircher lab for providing the data.
+</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>
+