Coevolutionary analyses require phylogenetically deep alignments and better null models to accurately detect inter-protein contacts within and between species

被引:10
|
作者
Avila-Herrera, Aram [1 ,2 ]
Pollard, Katherine S. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif San Francisco, Bioinformat Grad Program, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA
来源
BMC BIOINFORMATICS | 2015年 / 16卷
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Coevolution; Methods comparison; Inter-protein; Cross-species; Host-virus; Contact prediction; Protein interaction; COEVOLVING POSITIONS; HUMAN APOBEC3G; RESIDUE COEVOLUTION; MUTUAL INFORMATION; YEAST; 2-HYBRID; VIF PROTEIN; PREDICTION; IDENTIFICATION; COMPLEX; CONSERVATION;
D O I
10.1186/s12859-015-0677-y
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background: When biomolecules physically interact, natural selection operates on them jointly. Contacting positions in protein and RNA structures exhibit correlated patterns of sequence evolution due to constraints imposed by the interaction, and molecular arms races can develop between interacting proteins in pathogens and their hosts. To evaluate how well methods developed to detect coevolving residues within proteins can be adapted for cross-species, inter-protein analysis, we used statistical criteria to quantify the performance of these methods in detecting inter-protein residues within 8 angstroms of each other in the co-crystal structures of 33 bacterial protein interactions. We also evaluated their performance for detecting known residues at the interface of a host-virus protein complex with a partially solved structure. Results: Our quantitative benchmarking showed that all coevolutionary methods clearly benefit from alignments with many sequences. Methods that aim to detect direct correlations generally outperform other approaches. However, faster mutual information based methods are occasionally competitive in small alignments and with relaxed false positive rates. Two commonly used null distributions are anti-conservative and have high false positive rates in some scenarios, although the empirical distribution of scores performs reasonably well with deep alignments. Conclusions: We conclude that coevolutionary analysis of cross-species protein interactions holds great promise but requires sequencing many more species pairs.
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页数:18
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