{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T19:54:49Z","timestamp":1776887689845,"version":"3.51.2"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2008,5,30]],"date-time":"2008-05-30T00:00:00Z","timestamp":1212105600000},"content-version":"unspecified","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.1000069","type":"journal-article","created":{"date-parts":[[2008,5,29]],"date-time":"2008-05-29T23:29:31Z","timestamp":1212103771000},"page":"e1000069","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":308,"title":["A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation"],"prefix":"10.1371","volume":"4","author":[{"given":"Sean R.","family":"Eddy","sequence":"first","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2008,5,30]]},"reference":[{"key":"ref1","first-page":"356","article-title":"Biological sequence analysis: probabilistic models of proteins and nucleic acids","author":"R Durbin","year":"1998"},{"key":"ref2","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":"Nucl Acids Res"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1006\/jmbi.1994.1104","article-title":"Hidden Markov models in computational biology: applications to protein modeling.","volume":"235","author":"A Krogh","year":"1994","journal-title":"J Mol Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ng0294-119","article-title":"Issues in searching molecular sequence databases.","volume":"6","author":"SF Altschul","year":"1994","journal-title":"Nature Genetics"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/bib\/bbk001","article-title":"Statistical significance in biological sequence analysis.","volume":"7","author":"AY Mitrophanov","year":"2006","journal-title":"Brief Bioinform"},{"key":"ref6","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":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1073\/pnas.87.6.2264","article-title":"Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes.","volume":"87","author":"S Karlin","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5873","DOI":"10.1073\/pnas.90.12.5873","article-title":"Applications and statistics for multiple high-scoring segments in molecular sequences.","volume":"90","author":"S Karlin","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0076-6879(96)66029-7","article-title":"Local alignment statistics.","volume":"266","author":"SF Altschul","year":"1996","journal-title":"Meth Enzymol"},{"key":"ref10","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":"J Park","year":"1998","journal-title":"J Mol Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/bioinformatics\/bth090","article-title":"A comparison of scoring functions for protein sequence profile alignment.","volume":"20","author":"RC Edgar","year":"2004","journal-title":"Bioinformatics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.sbi.2005.05.005","article-title":"The limits of protein sequence comparison?","volume":"15","author":"WR Pearson","year":"2005","journal-title":"Curr Opin Struct Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/0022-2836(91)90193-A","article-title":"Amino acid substitution matrices from an information theoretic perspective.","volume":"219","author":"SF Altschul","year":"1991","journal-title":"J Mol Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF02458620","article-title":"Maximum likelihood estimation of the statistical distribution of Smith\u2013Waterman local sequence similarity scores.","volume":"54","author":"R Mott","year":"1992","journal-title":"Bull Math Biol"},{"key":"ref15","first-page":"52","article-title":"A statistical theory of sequence alignment with gaps.","volume":"6","author":"D Drasdo","year":"1998","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1089\/cmb.1999.6.91","article-title":"Approximate statistics of gapped alignments.","volume":"6","author":"R Mott","year":"1999","journal-title":"J Comput Biol"},{"key":"ref17","first-page":"211","article-title":"Rapid assessment of extremal statistics for gapped local alignment.","volume":"7","author":"R Olsen","year":"1999","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1006\/jmbi.2000.3875","article-title":"Accurate formula for P-values of gapped local sequence and profile alignments.","volume":"300","author":"R Mott","year":"2000","journal-title":"J Mol Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1214\/aos\/1015951993","article-title":"Approximate P-values for local sequence alignments.","volume":"28","author":"D Siegmund","year":"2000","journal-title":"The Annals of Statistics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/nar\/29.2.351","article-title":"The estimation of statistical parameters for local alignment score distributions.","volume":"29","author":"SF Altschul","year":"2001","journal-title":"Nucl Acids Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1089\/106652701753216530","article-title":"Approximate P-values for local sequence alignments: Numerical studies.","volume":"8","author":"JD Storey","year":"2001","journal-title":"J Comput Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/10665270252935449","article-title":"Rapid significance estimation in local sequence alignment with gaps.","volume":"9","author":"R Bundschuh","year":"2002","journal-title":"J Comput Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/cmb.2006.13.429","article-title":"A practical approach to significance assessment in alignment with gaps.","volume":"13","author":"N Chia","year":"2006","journal-title":"J Comput Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1089\/cmb.2006.13.882","article-title":"Robust E-values for gapped local alignments.","volume":"13","author":"D Metzler","year":"2006","journal-title":"J Comput Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"D247","DOI":"10.1093\/nar\/gkj149","article-title":"Pfam: clans, web tools and services.","volume":"34","author":"RD Finn","year":"2006","journal-title":"Nucl Acids Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"D257","DOI":"10.1093\/nar\/gkj079","article-title":"SMART 5: domains in the context of genomes and networks.","volume":"34","author":"I Letunic","year":"2006","journal-title":"Nucl Acids Res"},{"key":"ref27","first-page":"92","article-title":"Remote protein homology detection using hidden Markov models","author":"S Johnson","year":"2006"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1089\/10665270152530845","article-title":"Statistical significance of probabilistic sequence alignment and related local hidden Markov models.","volume":"8","author":"Y-K Yu","year":"2001","journal-title":"J Comput Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1093\/bioinformatics\/bti629","article-title":"Calibrating E-values for hidden Markov models using reverse-sequence null models.","volume":"21","author":"K Karplus","year":"2005","journal-title":"Bioinformatics"},{"key":"ref30","article-title":"HMMER - biosequence analysis using profile hidden Markov models.","author":"SR Eddy","year":"2007"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"reviews2002.1","DOI":"10.1186\/gb-2001-2-10-reviews2002","article-title":"Having a BLAST with bioinformatics (and avoiding BLASTphemy).","volume":"2","author":"A Pertsemlidis","year":"2001","journal-title":"Genome Biol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(02)00727-4","article-title":"Computational genomics of noncoding RNA genes.","volume":"109","author":"SR Eddy","year":"2002","journal-title":"Cell"},{"key":"ref33","first-page":"727","article-title":"Probability theory: the logic of science","author":"ET Jaynes","year":"2003"},{"key":"ref34","first-page":"628","article-title":"Information theory, inference, and learning algorithms","author":"DJC MacKay","year":"2003"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/protein\/8.10.999","article-title":"A reliable sequence alignment method based on probabilities of residue correspondences.","volume":"8","author":"S Miyazawa","year":"1995","journal-title":"Protein Eng"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/jtbi.1995.0085","article-title":"Alignment of molecular sequences seen as random path analysis.","volume":"174","author":"MQ Zhang","year":"1995","journal-title":"J Theor Biol"},{"key":"ref37","first-page":"44","article-title":"A sequence similarity search algorithm based on a probabilistic interpretation of an alignment scoring system.","volume":"4","author":"P Bucher","year":"1996","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/nar\/30.5.1268","article-title":"BALSA: Bayesian algorithm for local sequence alignment.","volume":"30","author":"BJ Webb","year":"2002","journal-title":"Nucl Acids Res"},{"key":"ref39","first-page":"375","article-title":"Statistics of extremes","author":"EJ Gumbel","year":"1958"},{"key":"ref40","first-page":"407","article-title":"Discovering simple DNA sequences by the algorithmic significance method.","volume":"9","author":"A Milosavljevi\u0107","year":"1993","journal-title":"Comput Applic Biosci"},{"key":"ref41","first-page":"191","article-title":"Scoring hidden Markov models.","volume":"13","author":"C Barrett","year":"1997","journal-title":"Comput Applic Biosci"},{"key":"ref42","first-page":"3","article-title":"Statistical significance and extremal ensemble of gapped local hybrid alignment.","author":"Y-K Yu","year":"2002"},{"key":"ref43","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":"K Karplus","year":"1998","journal-title":"Bioinformatics"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0022-2836(81)90087-5","article-title":"Identification of common molecular subsequences.","volume":"147","author":"TF Smith","year":"1981","journal-title":"J Mol Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1093\/nar\/gkm414","article-title":"The identification of complete domains within protein sequences using accurate E-values for semi-global alignment.","volume":"35","author":"MG Kann","year":"2007","journal-title":"Nucl Acids Res"},{"key":"ref46","first-page":"580","article-title":"Statistical models and methods for lifetime data","author":"JF Lawless","year":"1982"},{"key":"ref47","first-page":"327","article-title":"Dirichlet mixtures: a method for improving detection of weak but significant protein sequence homology.","volume":"12","author":"K Sj\u00f6lander","year":"1996","journal-title":"Comput Applic Biosci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1093\/nar\/29.14.2994","article-title":"Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.","volume":"29","author":"AA Sch\u00e4ffer","year":"2001","journal-title":"Nucl Acids Res"},{"key":"ref49","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":"M Madera","year":"2002","journal-title":"Nucl Acids Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1371\/journal.pcbi.0030056","article-title":"Query-dependent banding (QDB) for faster RNA similarity searches.","volume":"3","author":"EP Nawrocki","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1093\/bioinformatics\/17.12.1158","article-title":"Estimation of P-values for global alignments of protein sequences.","volume":"17","author":"C Webber","year":"2001","journal-title":"Bioinformatics"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1073\/pnas.84.5.1239","article-title":"Phase transitions in sequence matches and nucleic acid structure.","volume":"84","author":"MS Waterman","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1093\/bioinformatics\/18.6.864","article-title":"Hybrid alignment: high-performance with universal statistics.","volume":"18","author":"Y-K Yu","year":"2002","journal-title":"Bioinformatics"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"D237","DOI":"10.1093\/nar\/gkl951","article-title":"CDD: a conserved domain database for interactive domain family analysis.","volume":"35","author":"A Marchler-Bauer","year":"2007","journal-title":"Nucl Acids Res"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"15688","DOI":"10.1073\/pnas.2533904100","article-title":"The compositional adjustment of amino acid substitution matrices.","volume":"100","author":"Y-K Yu","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/bioinformatics\/15.1.38","article-title":"Bayesian inference on biopolymer models.","volume":"15","author":"JS Liu","year":"1999","journal-title":"Bioinformatics"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T05:54:55Z","timestamp":1589003695000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000069"}},"subtitle":[],"editor":[{"given":"Burkhard","family":"Rost","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2008,5,30]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2008,5,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000069","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,30]]}}}