Hilton Sarah K, Doud Michael B, Bloom Jesse D
Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Genome Sciences, University of Washington, Seattle, WA, United States of America.
PeerJ. 2017 Jul 31;5:e3657. doi: 10.7717/peerj.3657. eCollection 2017.
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.
最近,通过深度突变扫描实验测量所有氨基酸点突变对蛋白质的影响已成为可能。这些实验测量结果可以为自然界中基因进化的位点特异性系统发育替代模型提供信息。在此,我们描述了一种能有效使用此类替代模型进行分析的软件。该软件phydms可用于将深度突变扫描实验结果与自然界中基因的选择情况进行比较。给定用其他程序推断出的系统发育树拓扑结构,phydms能够严格比较同一基因上不同实验对实际自然选择的捕捉程度。它还能对深度突变扫描数据进行重新缩放,以考虑实验室和自然界中选择严格程度的差异。最后,phydms可以识别出在自然界中进化方式与实验室实验预期不同的位点。随着深度突变扫描实验数据越来越广泛,phydms将有助于对实验结果与塑造自然界进化的实际选择压力进行定量比较。