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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sequence Context-specific Profiles For Homology Searching
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Sequence Context-specific Profiles For Homology Searching

机译：用于同源搜索的序列特定于上下文的配置文件

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摘要

Sequence alignment and database searching are essential tools in biology because a protein's function can often be inferred from homologous proteins. Standard sequence comparison methods use substitution matrices to find the alignment with the best sum of similarity scores between aligned residues. These similarity scores do not take the local sequence context into account. Here, we present an approach that derives context-specific amino acid similarities from short windows centered on each query sequence residue. Our results demonstrate that the sequence context contains much more information about the expected mutations than just the residue itself. By employing our context-specific similarities (CS-BLAST) in combination with NCBI BLAST, we increase the sensitivity more than 2-fold on a difficult benchmark set, without loss of speed. Alignment quality is likewise improved significantly. Furthermore, we demonstrate considerable improvements when applying this paradigm to sequence profiles: Two iterations of CSI-BLAST, our context-specific version of PSI-BLAST, are more sensitive than 5 iterations of PSI-BLAST. The paradigm for biological sequence comparison presented here is very general. It can replace substitution matrices in sequence- and profile-based alignment and search methods for both protein and nucleotide sequences.
机译：序列比对和数据库搜索是生物学中必不可少的工具，因为蛋白质的功能通常可以从同源蛋白质中推断出来。标准序列比较方法使用置换矩阵来查找比对的残基之间具有最佳相似度总和的比对。这些相似性分数不考虑局部序列上下文。在这里，我们提出了一种方法，该方法从以每个查询序列残基为中心的短窗口中得出特定于上下文的氨基酸相似性。我们的结果表明，序列上下文包含有关预期突变的信息，而不仅仅是残基本身。通过结合使用上下文特定的相似性（CS-BLAST）和NCBI BLAST，我们在困难的基准测试集上将灵敏度提高了2倍以上，而不会降低速度。对准质量同样得到显着改善。此外，当将这种范例应用于序列配置文件时，我们展示了相当大的改进：CSI-BLAST的两次迭代（我们的上下文特定版本的PSI-BLAST）比PSI-BLAST的5次迭代更为敏感。这里介绍的用于生物序列比较的范例非常笼统。它可以替代基于蛋白质和核苷酸序列的基于序列和概况的比对和搜索方法中的替代矩阵。

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