{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:16:49Z","timestamp":1758709009033},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Recently developed profile\u2013profile methods rival structural comparisons in their ability to detect homology between distantly related proteins. Despite this tremendous progress, many genuine relationships between protein families cannot be recognized as comparisons of their profiles result in scores that are statistically insignificant.<\/jats:p><jats:p>Results: Using known evolutionary relationships among protein superfamilies in SCOP database, support vector machines were trained on four sets of discriminatory features derived from the output of HHsearch. Upon validation, it was shown that the automatic classification of all profile\u2013profile matches was superior to fixed threshold-based annotation in terms of sensitivity and specificity. The effectiveness of this approach was demonstrated by annotating several domains of unknown function from the Pfam database.<\/jats:p><jats:p>Availability: Programs and scripts implementing the methods described in this manuscript are freely available from http:\/\/hhsvm.dlakiclab.org\/.<\/jats:p><jats:p>Contact: \u00a0mdlakic@montana.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp555","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T01:21:44Z","timestamp":1253668904000},"page":"3071-3076","source":"Crossref","is-referenced-by-count":9,"title":["HHsvm: fast and accurate classification of profile\u2013profile matches identified by HHsearch"],"prefix":"10.1093","volume":"25","author":[{"given":"Mensur","family":"Dlaki\u0107","sequence":"first","affiliation":[{"name":"Department of Microbiology, Montana State University, Bozeman, MT 59717-3520, USA"}]}],"member":"286","published-online":{"date-parts":[[2009,9,22]]},"reference":[{"key":"2023013112154187300_B1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2023013112154187300_B2","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B3","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkm993","article-title":"Data growth and its impact on the SCOP database: new developments","volume":"36","author":"Andreeva","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B4","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1093\/nar\/28.18.3417","article-title":"Holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories","volume":"28","author":"Aravind","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B5","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1073\/pnas.95.11.6073","article-title":"Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationships","volume":"95","author":"Brenner","year":"1998","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023013112154187300_B6","author":"Chang","year":"2001","journal-title":"LIBSVM: a library for support vector machines."},{"key":"2023013112154187300_B7","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.jmb.2007.12.076","article-title":"Discrimination between distant homologs and structural analogs: lessons from manually constructed, reliable data sets","volume":"377","author":"Cheng","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2023013112154187300_B8","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B9","doi-asserted-by":"crossref","first-page":"D281","DOI":"10.1093\/nar\/gkm960","article-title":"The Pfam protein families database","volume":"36","author":"Finn","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B10","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/bioinformatics\/btm626","article-title":"Prediction of protein functional residues from sequence by probability density estimation","volume":"24","author":"Fischer","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B11","doi-asserted-by":"crossref","first-page":"W576","DOI":"10.1093\/nar\/gkh370","article-title":"Detecting distant homology with Meta-BASIC","volume":"32","author":"Ginalski","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/jmbi.1999.3091","article-title":"Protein secondary structure prediction based on position-specific scoring matrices","volume":"292","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2023013112154187300_B13","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/bioinformatics\/14.10.846","article-title":"Hidden Markov models for detecting remote protein homologies","volume":"14","author":"Karplus","year":"1998","journal-title":"Bioinformatics"},{"issue":"Suppl. 6","key":"2023013112154187300_B14","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/prot.10540","article-title":"Combining local-structure, fold-recognition, and new fold methods for protein structure prediction","volume":"53","author":"Karplus","year":"2003","journal-title":"Proteins"},{"key":"2023013112154187300_B15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1472-6807-7-40","article-title":"Realm of PD-(D\/E)XK nuclease superfamily revisited: detection of novel families with modified transitive meta profile searches","volume":"7","author":"Knizewski","year":"2007","journal-title":"BMC Struct. Biol."},{"key":"2023013112154187300_B16","first-page":"285","article-title":"Support vector machinery for infinite ensemble learning","volume":"9","author":"Lin","year":"2008","journal-title":"J. Mach. Learn. Res."},{"key":"2023013112154187300_B17","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1093\/nar\/gkf544","article-title":"A comparison of profile hidden Markov model procedures for remote homology detection","volume":"30","author":"Madera","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B18","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1093\/nar\/gkn175","article-title":"Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses","volume":"36","author":"Orlowski","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B19","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1006\/jmbi.1998.2221","article-title":"Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods","volume":"284","author":"Park","year":"1998","journal-title":"J. Mol. Biol."},{"key":"2023013112154187300_B20","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1073\/pnas.85.8.2444","article-title":"Improved tools for biological sequence comparison","volume":"85","author":"Pearson","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023013112154187300_B21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.7551\/mitpress\/1113.003.0008","article-title":"Probabilities for SV machines","volume-title":"Advances in Large Margin Classifiers.","author":"Platt","year":"2000"},{"key":"2023013112154187300_B22","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1093\/bioinformatics\/btm355","article-title":"Methods of remote homology detection can be combined to increase coverage by 10% in the midnight zone","volume":"23","author":"Reid","year":"2007","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/12.2.85","article-title":"Twilight zone of protein sequence alignments","volume":"12","author":"Rost","year":"1999","journal-title":"Protein Eng."},{"key":"2023013112154187300_B24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0022-2836(02)01371-2","article-title":"COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance","volume":"326","author":"Sadreyev","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2023013112154187300_B25","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1093\/nar\/18.20.6097","article-title":"Sequence logos: a new way to display consensus sequences","volume":"18","author":"Schneider","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B26","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1093\/bioinformatics\/bti434","article-title":"Visualizing profile-profile alignment: pairwise HMM logos","volume":"21","author":"Schuster-Bockler","year":"2005","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B27","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/bioinformatics\/btn028","article-title":"SVM-HUSTLE\u2013an iterative semi-supervised machine learning approach for pairwise protein remote homology detection","volume":"24","author":"Shah","year":"2008","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B28","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/bioinformatics\/bti125","article-title":"Protein homology detection by HMM-HMM comparison","volume":"21","author":"S\u00f6ding","year":"2005","journal-title":"Bioinformatics"},{"key":"2023013112154187300_B29","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023013112154187300_B30","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-2440-0","volume-title":"The Nature of Statistical Learning Theory","author":"Vapnik","year":"1995"},{"key":"2023013112154187300_B31","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1006\/jmbi.2001.5293","article-title":"Within the twilight zone: a sensitive profile-profile comparison tool based on information theory","volume":"315","author":"Yona","year":"2002","journal-title":"J. Mol. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/23\/3071\/48997680\/bioinformatics_25_23_3071.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/25\/23\/3071\/48997680\/bioinformatics_25_23_3071.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T18:11:07Z","timestamp":1710612667000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/25\/23\/3071\/215757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,22]]},"references-count":31,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2009,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btp555","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,12,1]]},"published":{"date-parts":[[2009,9,22]]}}}