Protein homology detection by HMM-HMM comparison
Protein homology detection by HMM-HMM comparison
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DOI：
10.1093/bioinformatics/bti125
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发表时间：
2005-04-01
期刊：
影响因子：
5.8
通讯作者：
Söding, J
中科院分区：
文献类型：
--
作者：
Söding, J
动机：蛋白质同源性检测和序列比对是基于蛋白质结构的预测，功能预测和进化。分子：我们已将蛋白序列与剖面隐藏的马尔可夫模型（HMM）的比对概括为谱图HMMS的成对比对。 。我们提出了一种基于这种方法来检测蛋白质之间遥远同源关系的方法。该方法（HHSearch）与Blast，Psi-Blast，Hmmer和Profile Profile比较工具PROF_SIM和COMPASS一起进行基准测试，在全部比较SCOP 1.63的3691蛋白质域的数据库中，与以下配对序列身份的比较20％。敏感性：当HMM中包含预测的二级结构时，HHSearch能够检测到2.7至4.2倍比PSI-Blast或Hmmer的同源物更多，而误报率为10％，比起指南针或Prof_SIM的同源物高1.44至1.9倍。对配置文件比较方法的改进的大约一半归因于使用配置文件HMM代替简单的配置文件。对齐质量：更高的灵敏度通过比对质量的提高反映出。 HHSearch产生的1.2、1.7和3.3倍的良好对齐（“平衡”得分> 0.3）是下一个最佳方法（Compass），以及1.6、2.9和9.4倍的比对，是家族，超级家族和折叠水平的1.6、2.9和9.4倍速度分别：HHSearch在AMD64 2GHz PC上扫描了33 s的3691个域的200个残基的查询。这比Prof_sim快10倍，比Compass快17倍。
Motivation: Protein homology detection and sequence alignment are at the basis of protein structure prediction, function prediction and evolution.Results: We have generalized the alignment of protein sequences with a profile hidden Markov model (HMM) to the case of pairwise alignment of profile HMMs. We present a method for detecting distant homologous relationships between proteins based on this approach. The method (HHsearch) is benchmarked together with BLAST, PSI-BLAST, HMMER and the profile-profile comparison tools PROF_SIM and COMPASS, in an all-against-all comparison of a database of 3691 protein domains from SCOP 1.63 with pairwise sequence identities below 20%.Sensitivity: When the predicted secondary structure is included in the HMMs, HHsearch is able to detect between 2.7 and 4.2 times more homologs than PSI-BLAST or HMMER and between 1.44 and 1.9 times more than COMPASS or PROF_SIM for a rate of false positives of 10%. Approximately half of the improvement over the profile-profile comparison methods is attributable to the use of profile HMMs in place of simple profiles.Alignment quality: Higher sensitivity is mirrored by an increased alignment quality. HHsearch produced 1.2, 1.7 and 3.3 times more good alignments ('balanced' score > 0.3) than the next best method (COMPASS), and 1.6, 2.9 and 9.4 times more than PSI-BLAST, at the family, superfamily and fold level, respectively.Speed: HHsearch scans a query of 200 residues against 3691 domains in 33 s on an AMD64 2GHz PC. This is 10 times faster than PROF_SIM and 17 times faster than COMPASS.