Using multiple interdependency to separate functional from phylogenetic correlations in protein alignments
Using multiple interdependency to separate functional from phylogenetic correlations in protein alignments
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DOI：
10.1093/bioinformatics/btg072
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发表时间：
2003-04-12
期刊：
影响因子：
5.8
通讯作者：
Lui, TWH
中科院分区：
文献类型：
--
作者：
Tillier, ERM;Lui, TWH
动机：同源蛋白质的多重序列比对对于推断它们的系统发育历史和揭示蛋白质中的重要功能区域是有用的。功能性限制可能导致序列中两个或更多个氨基酸的共变异，使得一个位点处的取代伴随着另一个位点处的补偿性取代。仅仅找到对齐中各站点之间的统计相关性是不够的，因为这些相关性可能是几个未确定原因的结果。特别是，系统发育聚类将导致许多强correlations.Results：一个程序的开发，以检测统计相关性源于功能相互作用，通过删除强大的系统发育信号，导致每个网站的相关性与许多其他的序列。我们的方法依赖于比对的准确性，但它不需要任何关于同源性或替换过程的假设。利用计算机模拟验证了该方法的有效性，并将其应用于预测Pfam比对数据库中氨基酸之间的功能相互作用。
Motivation: Multiple sequence alignments of homologous proteins are useful for inferring their phylogenetic history and to reveal functionally important regions in the proteins. Functional constraints may lead to co-variation of two or more amino acids in the sequence, such that a substitution at one site is accompanied by compensatory substitutions at another site. It is not sufficient to find the statistical correlations between sites in the alignment because these may be the result of several undetermined causes. In particular, phylogenetic clustering will lead to many strong correlations.Results: A procedure is developed to detect statistical correlations stemming from functional interaction by removing the strong phylogenetic signal that leads to the correlations of each site with many others in the sequence. Our method relies upon the accuracy of the alignment but it does not require any assumptions about the phylogeny or the substitution process. The effectiveness of the method was verified using computer simulations and then applied to predict functional interactions between amino acids in the Pfam database of alignments.