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  Protein homology detection by HMM-HMM comparison.

Söding, J. (2005). Protein homology detection by HMM-HMM comparison. Bioinformatics, 21(7), 951-960. doi:10.1093/bioinformatics/bti125.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0017-EC7A-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-C5A4-0
Genre: Journal Article

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Söding, J.1, Author              
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1Research Group of Computational Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1933286              

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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 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. Availability: HHsearch can be downloaded from http://www.protevo.eb.tuebingen.mpg.de/download/ together with up-to-date versions of SCOP and PFAM. A web server is available at http://www.protevo.eb.tuebingen.mpg.de/toolkit/index.php?view=hhpred

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Language(s): eng - English
 Dates: 2005
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1093/bioinformatics/bti125
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Title: Bioinformatics
Source Genre: Journal
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Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 21 (7) Sequence Number: - Start / End Page: 951 - 960 Identifier: ISSN: 1367-4803
CoNE: https://pure.mpg.de/cone/journals/resource/954926969991