Missense mutations change a single amino acid in a protein and make up a large fraction of the variants observed in human populations. Most have no known clinical significance, both because clinical data are limited and because the relationship between sequence change and protein function is complex. Computational approaches that model evolutionary conservation across species can estimate how much a given position tolerates change, since -residues critical to function tend to be highly conserved. EVE (Evolutionary model of -Variant Effect) formalizes this reasoning with a deep generative model trained entirely on -natural sequence variation, without any reliance on clinical labels. This track shows EVE -scores for all possible missense substitutions in 2,949 disease-associated proteins. +residues critical to function tend to be highly conserved. EVE (Evolutionary model of +Variant Effect) formalizes this reasoning with a deep generative model trained +entirely on natural sequence variation, without any reliance on clinical labels. This track shows +EVE scores for all possible missense substitutions in 2,949 disease-associated proteins.
Each entry spans one protein at its genomic locus. The heatmap columns correspond to individual amino acid positions in the protein, placed at the codon's genomic coordinate. The rows correspond to the 20 standard amino acids, ordered by amino acid class to match the MaveDB track. Each cell shows the EVE score for substituting the wildtype amino acid at that position with the row amino acid. Empty cells indicate the wildtype amino acid at a given position (no substitution) or positions for which no score is available.
Cells are colored on a gradient: @@ -81,36 +81,36 @@ target="_blank">our GitHub repository. Two proteins (G6PT1, UniProt O43826; and MAFIP, Q8WZ33) were excluded because their VCF coordinates mapped to assembly scaffolds (chrCHR_HG2217_PATCH and chrGL000194.1) absent from the standard hg38 assembly. The remaining 2,949 proteins covering approximately 1.7 million amino acid positions are included in this track.
The data can be explored interactively in table format with the Table Browser or the Data Integrator and exported from there to spreadsheet or tab-separated tables. From scripts, the data can be accessed through our API, track=eve.
For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from -our download +our download server. The file for this track is called eve.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, 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. +here. The tool can also be used to obtain features within a given range, e.g. bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/eve/eve.bb -chrom=chr17 -start=43000000 -end=43200000 stdout
The original annotation source data can be downloaded from https://evemodel.org/download/bulk.
Thanks to Jonathan Frazer, Pascal Notin, Mafalda Dias, and Debora S. Marks at Harvard Medical School and Yarin Gal at the University of Oxford for making the EVE scores publicly available at evemodel.org.