MTR-Viewer: identifying regions within genes under purifying selection.

Abstract:

:Advances in genomic sequencing have enormous potential to revolutionize personalized medicine, however distinguishing disease-causing from benign variants remains a challenge. The increasing number of human genome and exome sequences available has revealed areas where unfavourable variation is removed through purifying selection. Here, we present the MTR-Viewer, a web-server enabling easy visualization at the gene or variant level of the Missense Tolerance Ratio (MTR), a measure of regional intolerance to missense variation calculated using variation from 240 000 exome and genome sequences. The MTR-Viewer enables exploration of MTR calculations, using different sliding windows, for over 18 000 human protein-coding genes and 85 000 alternative transcripts. Users can also view MTR scores calculated for specific ethnicities, to enable easy exploration of regions that may be under different selective pressure. The spatial distribution of population and known disease variants is also displayed on the protein's domain structure. Intolerant regions were found to be highly enriched for ClinVar pathogenic and COSMIC somatic missense variants (Mann-Whitney U test P < 2.2 × 10-16). As the MTR is not biased by known domains and protein features, it can highlight functionally important regions within genes overlooked or inaccessible by traditional methods. MTR-Viewer is freely available via a user friendly web-server at http://biosig.unimelb.edu.au/mtr-viewer/.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Silk M,Petrovski S,Ascher DB

doi

10.1093/nar/gkz457

subject

Has Abstract

pub_date

2019-07-02 00:00:00

pages

W121-W126

issue

W1

eissn

0305-1048

issn

1362-4962

pii

5512091

journal_volume

47

pub_type

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