Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements
Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements
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DOI：
10.1093/nar/29.14.2994
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发表时间：
2001-07-15
影响因子：
14.9
通讯作者：
Altschul, SF
中科院分区：
文献类型：
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作者：
Schäffer, AA;Aravind, L;Altschul, SF
PSI-BLAST是一种迭代程序，用于在数据库中搜索与查询序列具有较远相似性的蛋白质。我们对PSI-BLAST中使用的方法进行了十几次修改，目的是提高找到真正阳性匹配的准确性。为了评估性能，我们使用了一组103个查询，其中酵母中的真正阳性已经由人类专家注释，以及一个流行的检索准确率(ROC)衡量标准，可以归一化为介于0(最差)和1(最好)之间的值。我们认为新颖的修改将ROC得分从0.758+/-0.005提高到0.895+/-0.003。这还不包括我们在“基线”版本中包含的四个修改的好处，即使它们没有在PSI-BLAST版本2.0中实现。准确率的提高在第二个小测试集上得到了证实。这项测试包括用非冗余蛋白质数据库中真正阳性的精选列表来分析三个蛋白质家族。改进的主要原因是，对于每个数据库序列，使用了与该序列的氨基酸组成相适应的特定位置评分系统。基于成分的统计的使用对于PSI-BLAST的大规模自动化应用特别有益。
PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST.