Phylogeny-independent detection of functional residues
Phylogeny-independent detection of functional residues
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DOI：
10.1093/bioinformatics/btl104
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发表时间：
2006-06-15
期刊：
影响因子：
5.8
通讯作者：
Valencia, Alfonso
中科院分区：
文献类型：
--
作者：
Pazos, Florencio;Rausell, Antonio;Valencia, Alfonso
动机：目前对蛋白质组进行大规模表征的项目是生成功能未知的蛋白质序列和结构。实验确定功能重要部位的困难要求发展计算方法。第一种技术是基于在多序列比对（msa）中搜索完全保守位置，其次是定位家族相关保守位置的方法。这些依赖于定位这些与功能特异性相关的位置的排列中隐含的功能分类。下一个明显的步骤，仍然很少探索，是使用不同于隐含在蛋白质之间的序列关系的功能分类来检测这些位置。在这里，我们提出了两种定位功能位置的新方法，这些方法可以结合任意的外部功能分类，这些分类可能与MSA中隐含的分类一致，也可能不一致。Xdet方法能够使用具有相关层次结构的功能分类或函数之间的相似性来定位与该分类相关的位置。MCdet方法使用多元统计分析来定位多功能家族中负责每种功能的位置。结果：我们将该方法应用于不同的情况，说明了功能关系和系统发育关系之间存在分歧的情况，并证明了它们对于独立于系统发育的功能位置预测的有效性。
Motivation: Current projects for the massive characterization of proteomes are generating protein sequences and structures with unknown function. The difficulty of experimentally determining functionally important sites calls for the development of computational methods. The first techniques, based on the search for fully conserved positions in multiple sequence alignments (MSAs), were followed by methods for locating family-dependent conserved positions. These rely on the functional classification implicit in the alignment for locating these positions related with functional specificity. The next obvious step, still scarcely explored, is to detect these positions using a functional classification different from the one implicit in the sequence relationships between the proteins. Here, we present two new methods for locating functional positions which can incorporate an arbitrary external functional classification which may or may not coincide with the one implicit in the MSA. The Xdet method is able to use a functional classification with an associated hierarchy or similarity between functions to locate positions related to that classification. The MCdet method uses multivariate statistical analysis to locate positions responsible for each one of the functions within a multifunctional family.Results: We applied the methods to different cases, illustrating scenarios where there is a disagreement between the functional and the phylogenetic relationships, and demonstrated their usefulness for the phylogeny-independent prediction of functional positions.