DMCA
Protein homology detection by HMM-HMM comparison (2005)
| Venue: | BIOINFORMATICS |
| Citations: | 398 - 8 self |
BibTeX
@ARTICLE{Söding05proteinhomology,
author = {Johannes Söding},
title = {Protein homology detection by HMM-HMM comparison},
journal = {BIOINFORMATICS},
year = {2005},
pages = {951--960}
}
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Abstract
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 se-quences 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 compari-son of a database of 3691 protein domains from SCOP 1.63 with pairwise sequence identities below 20%. Sensitivity: When 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%. Approxi-mately half of the improvement over the profile–profile com-parison methods is attributable to the use of profile HMMs in place of simple profiles. Alignment quality: Higher sensitivity is mirrored by an in-creased 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, super-family, and fold level. Speed: HHsearch scans a query of 200 residues against 3691 domains in 33s on an AMD64 3GHz PC. This is 10 times faster than PROF_SIM and 17 times faster than
Keyphrases
protein homology detection hmm-hmm comparison profile hmms sequence alignment profile-profile comparison tool prof_sim approxi-mately half pairwise alignment protein se-quences distant homologous relationship alignment quality in-creased alignment quality protein structure prediction simple profile next best method profile hidden markov model false positive pairwise sequence identity secondary structure all-against-all compari-son profile profile com-parison method function prediction fold level good alignment
