This track collection shows Rare Exome Variant Ensemble Learner (REVEL) scores for predicting the deleteriousness of each nucleotide change in the genome.
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.
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.
Single nucleotide variants (SNV): For SNVs, 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.
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 instead of an actual score, the tooltip text will show
the average score of all nucleotides under the cursor. This is indicated by
the prefix "~" in the mouseover. Averages of scores are not useful for any
application of REVEL.
REVEL scores are available at the REVEL website. The site provides precomputed REVEL scores for all possible human missense variants -to facilitate the identification of pathogenic variants amoung the large number of +to facilitate the identification of pathogenic variants among the large number of rare variants discovered in sequencing studies.
The REVEL data on the UCSC Genome Browser can be explored interactively with the
Table Browser or the
Data Integrator.
For automated download and analysis, the genome annotation is stored at UCSC in bigWig
files that can be downloaded from
our download server.
The files for this track are called a.bw, c.bw, g.bw, t.bw. Individual
regions or the whole genome annotation can be obtained using our tool bigWigToWig
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
here.
The tools can also be used to obtain features confined to given range, e.g.
bigWigToBedGraph -chrom=chr1 -start=100000 -end=100500 http://hgdownload.soe.ucsc.edu/gbdb/$db/revel/a.bw stdout
Data were converted from the files provided on the REVEL Downloads website.
Thanks to the REVEL development team for providing precomputed data.
Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, Musolf A, Li Q, Holzinger E, Karyadi D, et al. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants Am J Hum Genet. 2016 Oct 6;99(4):877-885. PMID: 27666373; PMC: PMC5065685