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Cited by 2,423

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Protein homology detection by HMM–HMM comparison

Open access
Söding, Johannes·2005·Bioinformatics

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 Contact: johannes.soeding@tuebingen.mpg.de

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Crossref · 10.1093/bioinformatics/bti125

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Metadata

Authors
Söding, J.
Venue
Bioinformatics
Published
2004-11-05
Volume
21
Issue
7
Pages
951-960
ISSN
  • 1367-4803 (ISSN-L)
  • 1367-4811
OpenAlex
W2145268834
Cited by
2,423
References
3
FWCI
12.68
Type
journal article
Language
en
Open access
bronze

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