Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods
Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods
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DOI：
10.1006/jmbi.1998.2221
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发表时间：
1998-12-11
影响因子：
5.6
通讯作者：
Chothia, C
中科院分区：
文献类型：
--
作者：
Park, J;Karplus, K;Chothia, C
相关蛋白质的序列可以偏离它们的关系可以通过成对序列比较来识别的点。为了克服这一限制，已经开发了用作查询的方法，这些方法不是单个序列，而是相关序列的集合或由相关序列共享的特征的表示。这里，我们描述了对这些方法中的三种方法的评估：隐藏马尔可夫模型过程的SAM-T98实现；PSI-BLAST；以及中间序列搜索(ISS)过程。我们确定了这些程序可以在多大程度上检测序列数据库PDBD40-J成员之间的进化关系。这个数据库源于蛋白质结构分类(SCOP)，包含了结构已知的蛋白质序列，它们之间的序列同源性不超过40%。通过对它们的结构细节以及在许多情况下它们的功能特征的检查，发现了那些具有低序列同一性的基因之间存在的进化关系。对于可能的432,680个假阳性预测中的9个，即假阳性率约为1/50，SAM-T98在PDBD40-J中找到了35%的真实同源关系，而PSI-BLAST发现了30%，ISS发现了25%。总体而言，这大约是通过成对比较程序FASTA(17%)和GAP-BLAST(15%)可以检测到的PDBD40-J关系数量的两倍。对于PDBD40-J中的远相关序列，序列同源性小于30%的序列对，SAM-T98和PSI-BLAST检测到的关系数是成对方法发现的关系数的三倍。(C)1998年学术出版社。
The sequences of related proteins can diverge beyond the point where their relationship can be recognised by pairwise sequence comparisons. In attempts to overcome this limitation, methods have been developed that use as a query, not a single sequence, but sets of related sequences or a representation of the characteristics shared by related sequences. Here we describe an assessment of three of these methods: the SAM-T98 implementation of a hidden Markov model procedure; PSI-BLAST; and the intermediate sequence search (ISS) procedure. We determined the extent to which these procedures can detect evolutionary relationships between the members of the sequence database PDBD40-J. This database, derived from the structural classification of proteins (SCOP), contains the sequences of proteins of known structure whose sequence identities with each other are 40% or less. The evolutionary relationships that exist between those that have low sequence identities were found by the examination of their structural details and, in many cases, their functional features. For nine false positive predictions out of a possible 432,680, i.e. at a false positive rate of about 1/50,000, SAM-T98 found 35% of the true homologous relationships in PDBD40-J, whilst PSI-BLAST found 30% and ISS found 25%. Overall, this is about twice the number of PDBD40-J relations that can be detected by the pairwise comparison procedures FASTA (17%) and GAP-BLAST (15%). For distantly related sequences in PDBD40-J, those pairs whose sequence identity is less than 30%, SAM-T98 and PSI-BLAST detect three times the number of relationships found by the pairwise methods. (C) 1998 Academic Press.