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PeerJ. 2017 Jul 31;5:e3657. doi: 10.7717/peerj.3657. eCollection 2017.

phydms: software for phylogenetic analyses informed by deep mutational scanning.

Hilton SK1,2, Doud MB1,2,3, Bloom JD1,2.

Author information

1
Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
2
Department of Genome Sciences, University of Washington, Seattle, WA, United States of America.
3
Medical Scientist Training Program, University of Washington, Seattle, WA, United States of America.

Abstract

It has recently become possible to experimentally measure the effects of all amino-acid point mutations to proteins using deep mutational scanning. These experimental measurements can inform site-specific phylogenetic substitution models of gene evolution in nature. Here we describe software that efficiently performs analyses with such substitution models. This software, phydms, can be used to compare the results of deep mutational scanning experiments to the selection on genes in nature. Given a phylogenetic tree topology inferred with another program, phydms enables rigorous comparison of how well different experiments on the same gene capture actual natural selection. It also enables re-scaling of deep mutational scanning data to account for differences in the stringency of selection in the lab and nature. Finally, phydms can identify sites that are evolving differently in nature than expected from experiments in the lab. As data from deep mutational scanning experiments become increasingly widespread, phydms will facilitate quantitative comparison of the experimental results to the actual selection pressures shaping evolution in nature.

KEYWORDS:

Amino acid preferences; Beta lactamase; Codon substitution model; Deep mutational scanning; Diversifying selection; ExpCM; Hemagglutinin; Phylogenetics; Positive selection; dN/dS

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