Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Inferring the molecular and phenotypic impact of amino acid variants with MutPred2

Pejaver, Vikas, Urresti, Jorge, Lugo-Martinez, Jose, Pagel, Kymberleigh A., Lin, Guan Ning, Nam, Hyun-Jun, Mort, Matthew, Cooper, David N. ORCID:, Sebat, Jonathan, Iakoucheva, Lilia M., Mooney, Sean D. and Radivojac, Predrag 2020. Inferring the molecular and phenotypic impact of amino acid variants with MutPred2. Nature Communications 11 (1) , 5918. 10.1038/s41467-020-19669-x

[thumbnail of MORT, Matthew - Inferring the molecular and phenotypic impact of amino acid variants with MutPred2.pdf]
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview


Identifying pathogenic variants and underlying functional alterations is challenging. To this end, we introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions over existing methods, generates molecular mechanisms potentially causative of disease, and returns interpretable pathogenicity score distributions on individual genomes. Whilst its prioritization performance is state-of-the-art, a distinguishing feature of MutPred2 is the probabilistic modeling of variant impact on specific aspects of protein structure and function that can serve to guide experimental studies of phenotype-altering variants. We demonstrate the utility of MutPred2 in the identification of the structural and functional mutational signatures relevant to Mendelian disorders and the prioritization of de novo mutations associated with complex neurodevelopmental disorders. We then experimentally validate the functional impact of several variants identified in patients with such disorders. We argue that mechanism-driven studies of human inherited disease have the potential to significantly accelerate the discovery of clinically actionable variants.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 8 February 2021
Date of Acceptance: 23 October 2020
Last Modified: 27 Nov 2022 13:22

Citation Data

Cited 101 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics