A statistical score for assessing the quality of multiple sequence alignments.

A statistical score for assessing the quality of multiple sequence alignments.
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DOI:
10.1186/1471-2105-7-484
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发表时间:
2006-11-03
期刊:
影响因子:
3
通讯作者:
Uusipaikka E
Uusipaikka E
中科院分区:
生物学4区
文献类型:
--
作者:
Ahola V;Aittokallio T;Vihinen M;Uusipaikka E

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多序列比对是生物信息学中许多重要应用的基础,旨在检测功能重要区域、预测蛋白质结构、构建系统发育树等。尽管对一组远程相关序列进行多序列比对的自动构建是一项非常具有挑战性且容易出错的任务,但许多下游分析仍然严重依赖比对的准确性。为了解决对客观评估框架的需求,我们引入了一个统计分数来评估给定多序列比对的质量。质量评估是基于使用重要抽样方法结合统计轮廓分析框架计算对齐中显著保守位置的数量。我们首先评估了用于测量位置守恒的对准质量分数的一个新的目标函数。Src同源性2 (SH2)结构域、ras样蛋白、肽酶M13、枯草酶和β-内酰胺酶家族的结果表明,该评分可以区分不同保守程度的序列模式。其次,我们利用一种新的比对质量评分和常用的对和方法,对几种广泛使用的多序列比对方案所产生的比对质量进行了评价。根据这些结果,Mafft策略L-INS-i优于其他方法,尽管Probcons, TCoffee和Muscle之间的差异几乎不显著。新的对齐质量评分提供了类似的结果比对和方法。结果表明,所提出的统计分数可用于评估多序列比对的质量。
Multiple sequence alignment is the foundation of many important applications in bioinformatics that aim at detecting functionally important regions, predicting protein structures, building phylogenetic trees etc. Although the automatic construction of a multiple sequence alignment for a set of remotely related sequences cause a very challenging and error-prone task, many downstream analyses still rely heavily on the accuracy of the alignments. To address the need for an objective evaluation framework, we introduce a statistical score that assesses the quality of a given multiple sequence alignment. The quality assessment is based on counting the number of significantly conserved positions in the alignment using importance sampling method in conjunction with statistical profile analysis framework. We first evaluate a novel objective function used in the alignment quality score for measuring the positional conservation. The results for the Src homology 2 (SH2) domain, Ras-like proteins, peptidase M13, subtilase and β-lactamase families demonstrate that the score can distinguish sequence patterns with different degrees of conservation. Secondly, we evaluate the quality of the alignments produced by several widely used multiple sequence alignment programs using a novel alignment quality score and a commonly used sum of pairs method. According to these results, the Mafft strategy L-INS-i outperforms the other methods, although the difference between the Probcons, TCoffee and Muscle is mostly insignificant. The novel alignment quality score provides similar results than the sum of pairs method. The results indicate that the proposed statistical score is useful in assessing the quality of multiple sequence alignments.
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