{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:08:56Z","timestamp":1775840936246,"version":"3.50.1"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T00:00:00Z","timestamp":1389830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003440","type":"journal-article","created":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T16:16:32Z","timestamp":1389888992000},"page":"e1003440","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":739,"title":["PredictSNP: Robust and Accurate Consensus Classifier for Prediction of Disease-Related Mutations"],"prefix":"10.1371","volume":"10","author":[{"given":"Jaroslav","family":"Bendl","sequence":"first","affiliation":[]},{"given":"Jan","family":"Stourac","sequence":"additional","affiliation":[]},{"given":"Ondrej","family":"Salanda","sequence":"additional","affiliation":[]},{"given":"Antonin","family":"Pavelka","sequence":"additional","affiliation":[]},{"given":"Eric D.","family":"Wieben","sequence":"additional","affiliation":[]},{"given":"Jaroslav","family":"Zendulka","sequence":"additional","affiliation":[]},{"given":"Jan","family":"Brezovsky","sequence":"additional","affiliation":[]},{"given":"Jiri","family":"Damborsky","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2014,1,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1101\/gr.8.12.1229","article-title":"A DNA polymorphism discovery resource for research on human genetic variation","volume":"8","author":"FS Collins","year":"1998","journal-title":"Genome Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"GR Abecasis","year":"2010","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1126\/science.278.5343.1580","article-title":"Variations on a theme: cataloging human DNA sequence variation","volume":"278","author":"FS Collins","year":"1997","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1126\/science.273.5281.1516","article-title":"The future of genetic studies of complex human diseases","volume":"273","author":"N Risch","year":"1996","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1042\/BJ20121221","article-title":"Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes","volume":"449","author":"RA Studer","year":"2013","journal-title":"Biochem J"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/10290","article-title":"Characterization of single-nucleotide polymorphisms in coding regions of human genes","volume":"22","author":"M Cargill","year":"1999","journal-title":"Nat Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/10297","article-title":"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis","volume":"22","author":"MK Halushka","year":"1999","journal-title":"Nat Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/bib\/bbq007","article-title":"A guide to web tools to prioritize candidate genes","volume":"12","author":"L-C Tranchevent","year":"2011","journal-title":"Brief Bioinform"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/bib\/bbr070","article-title":"Bioinformatics for personal genome interpretation","volume":"13","author":"E Capriotti","year":"2012","journal-title":"Brief Bioinform"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1093\/bioinformatics\/btp528","article-title":"Automated inference of molecular mechanisms of disease from amino acid substitutions","volume":"25","author":"B Li","year":"2009","journal-title":"Bioinforma Oxf Engl"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"W480","DOI":"10.1093\/nar\/gki372","article-title":"nsSNPAnalyzer: identifying disease-associated nonsynonymous single nucleotide polymorphisms","volume":"33","author":"L Bao","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1093\/nar\/gkf493","article-title":"Human non-synonymous SNPs: server and survey","volume":"30","author":"V Ramensky","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"IA Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1093\/nar\/gkm238","article-title":"SNAP: predict effect of non-synonymous polymorphisms on function","volume":"35","author":"Y Bromberg","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1101\/gr.3804205","article-title":"Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity","volume":"15","author":"EA Stone","year":"2005","journal-title":"Genome Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"15398","DOI":"10.1073\/pnas.0404380101","article-title":"Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: Evolutionary evidence for differences in molecular effects","volume":"101","author":"PD Thomas","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1093\/bioinformatics\/btl423","article-title":"Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information","volume":"22","author":"E Capriotti","year":"2006","journal-title":"Bioinformatics"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: Predicting amino acid changes that affect protein function","volume":"31","author":"PC Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/humu.21047","article-title":"Functional annotations improve the predictive score of human disease-related mutations in proteins","volume":"30","author":"R Calabrese","year":"2009","journal-title":"Hum Mutat"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/bib\/bbn047","article-title":"Next generation tools for the annotation of human SNPs","volume":"10","author":"R Karchin","year":"2009","journal-title":"Brief Bioinform"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev.genom.7.080505.115630","article-title":"Predicting the effects of amino acid substitutions on protein function","volume":"7","author":"PC Ng","year":"2006","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/bib\/bbq073","article-title":"An empirical assessment of validation practices for molecular classifiers","volume":"12","author":"PJ Castaldi","year":"2011","journal-title":"Brief Bioinform"},{"key":"ref23","unstructured":"Baldi P, Brunak S (2001) Bioinformatics: The machine learning approach. CambridgeMA: MIT Press. 492 p."},{"key":"ref24","doi-asserted-by":"crossref","first-page":"7332","DOI":"10.1200\/JCO.2005.02.8712","article-title":"Roadmap for developing and validating therapeutically relevant genomic classifiers","volume":"23","author":"R Simon","year":"2005","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/humu.21445","article-title":"Performance of mutation pathogenicity prediction methods on missense variants","volume":"32","author":"J Thusberg","year":"2011","journal-title":"Hum Mutat"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1109\/MCAS.2006.1688199","article-title":"Ensemble based systems in decision making","volume":"6","author":"R Polikar","year":"2006","journal-title":"IEEE Circuits Syst Mag"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.ajhg.2011.03.004","article-title":"Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel","volume":"88","author":"A Gonz\u00e1lez-P\u00e9rez","year":"2011","journal-title":"Am J Hum Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/humu.22102","article-title":"PON-P: Integrated predictor for pathogenicity of missense variants","volume":"33","author":"A Olatubosun","year":"2012","journal-title":"Hum Mutat"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2164-14-S3-S2","article-title":"Collective judgment predicts disease-associated single nucleotide variants","volume":"14","author":"E Capriotti","year":"2013","journal-title":"BMC Genomics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/nar\/27.1.355","article-title":"The Protein Mutant Database","volume":"27","author":"T Kawabata","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"ref31","first-page":"D71","article-title":"Reorganizing the protein space at the Universal Protein Resource (UniProt)","volume":"40","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/hmg\/10.6.591","article-title":"Prediction of deleterious human alleles","volume":"10","author":"S Sunyaev","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"W376","DOI":"10.1093\/nar\/gkp410","article-title":"HotSpot Wizard: a web server for identification of hot spots in protein engineering","volume":"37","author":"A Pavelka","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref34","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":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"D5","DOI":"10.1093\/nar\/gkp967","article-title":"Database resources of the National Center for Biotechnology Information","volume":"38","author":"EW Sayers","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/bioinformatics\/btq003","article-title":"CD-HIT Suite: a web server for clustering and comparing biological sequences","volume":"26","author":"Y Huang","year":"2010","journal-title":"Bioinformatics"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/1471-2105-5-113","article-title":"MUSCLE: a multiple sequence alignment method with reduced time and space complexity","volume":"5","author":"RC Edgar","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/10665270252935494","article-title":"A structural EM algorithm for phylogenetic inference","volume":"9","author":"N Friedman","year":"2002","journal-title":"J Comput Biol J Comput Mol Cell Biol"},{"key":"ref39","first-page":"Unit1.13","article-title":"The Human Gene Mutation Database (HGMD) and its exploitation in the fields of personalized genomics and molecular evolution","volume":"1","author":"PD Stenson","year":"2012","journal-title":"Curr Protoc Bioinforma Chapter"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/humu.20484","article-title":"PhenCode: connecting ENCODE data with mutations and phenotype","volume":"28","author":"B Giardine","year":"2007","journal-title":"Hum Mutat"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/humu.20405","article-title":"Immunodeficiency mutation databases (IDbases)","volume":"27","author":"H Piiril\u00e4","year":"2006","journal-title":"Hum Mutat"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"D187","DOI":"10.1093\/nar\/gkj161","article-title":"The Universal Protein Resource (UniProt): an expanding universe of protein information","volume":"34","author":"CH Wu","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1534\/genetics.104.039107","article-title":"The exchangeability of amino acids in proteins","volume":"170","author":"LY Yampolsky","year":"2005","journal-title":"Genetics"},{"key":"ref44","unstructured":"Aehle W, Cascao-Pereira LG, Estell DA, Goedegebuur F, Kellis JJT, <etal>et al<\/etal>.. (2010) Compositions and methods comprising serine protease variants."},{"key":"ref45","unstructured":"Cuevas WA, Estell DE, Hadi SH, Lee S-K, Ramer SW, <etal>et al<\/etal>.. (2009) Geobacillus Stearothermophilus Alpha-Amylase (AmyS) Variants with Improved Properties."},{"key":"ref46","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA data mining software: an update","volume":"11","author":"M Hall","year":"2009","journal-title":"SIGKDD Explor Newsl"},{"key":"ref47","unstructured":"John GH, Langley P (1995) Estimating continuous distributions in Bayesian classifiers. Proceedings of the Eleventh conference on Uncertainty in artificial intelligence. UAI&apos;95. San Francisco, CA, USA: Morgan Kaufmann Publishers Inc. pp. 338\u2013345. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dl.acm.org\/citation.cfm?id=2074158.2074196\" xlink:type=\"simple\">http:\/\/dl.acm.org\/citation.cfm?id=2074158.2074196<\/ext-link>. Accessed 25 June 2013."},{"key":"ref48","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2307\/2347628","article-title":"Ridge estimators in logistic regression","volume":"41","author":"L Cessie","year":"1992","journal-title":"Appl Stat"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1023\/A:1007662407062","article-title":"Large margin classification using the perceptron algorithm","volume":"37","author":"Y Freund","year":"1999","journal-title":"Mach Learn"},{"key":"ref50","first-page":"27:1","article-title":"LIBSVM: A library for support vector machines","volume":"2","author":"C-C Chang","year":"2011","journal-title":"ACM Trans Intell Syst Technol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF00153759","article-title":"Instance-based learning algorithms","volume":"6","author":"DW Aha","year":"1991","journal-title":"Mach Learn"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"L Breiman","year":"2001","journal-title":"Mach Learn"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"D189","DOI":"10.1093\/nar\/gkh034","article-title":"The ASTRAL Compendium in 2004","volume":"32","author":"J-M Chandonia","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1101\/gr.772403","article-title":"PANTHER: A Library of protein families and subfamilies indexed by function","volume":"13","author":"PD Thomas","year":"2003","journal-title":"Genome Res"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/bib\/bbk007","article-title":"Machine learning in bioinformatics","volume":"7","author":"P Larra\u00f1aga","year":"2006","journal-title":"Brief Bioinform"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/bioinformatics\/16.5.412","article-title":"Assessing the accuracy of prediction algorithms for classification: An overview","volume":"16","author":"P Baldi","year":"2000","journal-title":"Bioinformatics"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrg3046","article-title":"Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data","volume":"12","author":"GM Cooper","year":"2011","journal-title":"Nat Rev Genet"},{"key":"ref58","first-page":"3574","article-title":"OWL\u2013a non-redundant composite protein sequence database","volume":"22","author":"AJ Bleasby","year":"1994","journal-title":"Nucleic Acids Res"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: predicting effects of amino acid substitutions on proteins","volume":"40","author":"N-L Sim","year":"2012","journal-title":"Nucleic Acids Res"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T14:23:41Z","timestamp":1565101421000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003440"}},"subtitle":[],"editor":[{"given":"Paul P.","family":"Gardner","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2014,1,16]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003440","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,16]]}}}