DeMaSk: A deep mutational scanning substitution matrix and its use for variant impact prediction

Daniel Munro, Mona Singh

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Motivation: Accurately predicting the quantitative impact of a substitution on a protein's molecular function would be a great aid in understanding the effects of observed genetic variants across populations. While this remains a challenging task, new approaches can leverage data from the increasing numbers of comprehensive deep mutational scanning (DMS) studies that systematically mutate proteins and measure fitness. Results: We introduce DeMaSk, an intuitive and interpretable method based only upon DMS datasets and sequence homologs that predicts the impact of missense mutations within any protein. DeMaSk first infers a directional amino acid substitution matrix from DMS datasets and then fits a linear model that combines these substitution scores with measures of per-position evolutionary conservation and variant frequency across homologs. Despite its simplicity, DeMaSk has state-of-the-art performance in predicting the impact of amino acid substitutions, and can easily and rapidly be applied to any protein sequence.

Original languageEnglish (US)
Pages (from-to)5322-5329
Number of pages8
JournalBioinformatics
Volume36
Issue number22-23
DOIs
StatePublished - Dec 1 2020

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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