{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:05:28Z","timestamp":1778058328791,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: mRNA sequences and expressed sequence tags represent some of the most abundant experimental data for identifying genes and alternatively spliced products in metazoans. These transcript sequences are frequently studied by aligning them to a genomic sequence template. For existing programs, error-prone, polymorphic and cross-species data, as well as non-canonical splice sites, still present significant barriers to producing accurate, complete alignments.<\/jats:p>\n               <jats:p>Results: We took a novel approach to spliced alignment that meaningfully combined information from sequence similarity with that obtained from PSSM splice site models. Scoring systems were chosen to maximize their power of discrimination, and dynamic programming (DP) was employed to guarantee optimal solutions would be found. The resultant program, EXALIN, performed better than other popular tools tested under a wide range of conditions that included detection of micro-exons and human\u2013mouse cross-species comparisons. For improved speed with only a marginal decrease in splice site prediction accuracy, EXALIN could perform limited DP guided by a result from BLASTN.<\/jats:p>\n               <jats:p>Availability: The source code, binaries, scripts, scoring matrices and splice site models for human, mouse, rice and Caenorhabditis elegans utilized in this study are posted at . The software (scripts, source code and binaries) is copyrighted but free for all to use.<\/jats:p>\n               <jats:p>Contact: \u00a0gish@blast.wustl.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti748","type":"journal-article","created":{"date-parts":[[2005,11,3]],"date-time":"2005-11-03T01:13:48Z","timestamp":1130980428000},"page":"13-20","source":"Crossref","is-referenced-by-count":20,"title":["Improved spliced alignment from an information theoretic approach"],"prefix":"10.1093","volume":"22","author":[{"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Genetics, School of Medicine, Washington University in St Louis 1 \u00a0 1 \u00a0 \u00a0 4566 Scott Avenue, St Louis, MO 63110, USA"},{"name":"Department of Biomedical Engineering, School of Engineering, Washington University in St Louis 2 \u00a0 2 \u00a0 \u00a0 1 Brookings Drive, St Louis, MO 63130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren","family":"Gish","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine, Washington University in St Louis 1 \u00a0 1 \u00a0 \u00a0 4566 Scott Avenue, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,11,2]]},"reference":[{"key":"2023012408310121100_b1","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":"Altschul","year":"1991","journal-title":"J. Mol. Biol."},{"key":"2023012408310121100_b2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0076-6879(96)66029-7","article-title":"Local alignment statistics","volume":"266","author":"Altschul","year":"1996","journal-title":"Methods Enzymol."},{"key":"2023012408310121100_b3","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":"2023012408310121100_b4","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":"2023012408310121100_b5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1101\/gr.8.4.362","article-title":"Analysis of EST-driven gene annotation in human genomic sequence","volume":"8","author":"Bailey","year":"1998","journal-title":"Genome Res."},{"key":"2023012408310121100_b6","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/bioinformatics\/16.11.1040","article-title":"MaskerAid: a performance enhancement to RepeatMasker","volume":"16","author":"Bedell","year":"2000","journal-title":"Bioinformatics"},{"key":"2023012408310121100_b7","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/0022-2836(87)90354-8","article-title":"Selection of DNA binding sites by regulatory proteins. Statistical-mechanical theory and application to operators and promoters","volume":"193","author":"Berg","year":"1987","journal-title":"J. Mol. Biol."},{"key":"2023012408310121100_b8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0092-8674(00)00128-8","article-title":"Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology","volume":"103","author":"Black","year":"2000","journal-title":"Cell"},{"key":"2023012408310121100_b9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0014-5793(00)01581-7","article-title":"EST comparison indicates 38% of human mRNAs contain possible alternative splice forms","volume":"474","author":"Brett","year":"2000","journal-title":"FEBS Lett."},{"key":"2023012408310121100_b10","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/6851","article-title":"Reliable identification of large numbers of candidate SNPs from public EST data","volume":"21","author":"Buetow","year":"1999","journal-title":"Nat. Genet."},{"key":"2023012408310121100_b11","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.1093\/nar\/28.21.4364","article-title":"Analysis of canonical and non-canonical splice sites in mammalian genomes","volume":"28","author":"Burset","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023012408310121100_b12","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1093\/nar\/30.11.2478","article-title":"Fast algorithms for large-scale genome alignment and comparison","volume":"30","author":"Delcher","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012408310121100_b13","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1101\/gr.8.9.967","article-title":"A computer program for aligning a cDNA sequence with a genomic DNA sequence","volume":"8","author":"Florea","year":"1998","journal-title":"Genome Res."},{"key":"2023012408310121100_b14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1101\/gr.2889405","article-title":"Gene and alternative splicing annotation with AIR","volume":"15","author":"Florea","year":"2005","journal-title":"Genome Res."},{"key":"2023012408310121100_b15","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0168-9525(00)02093-X","article-title":"Repbase update: a database and an electronic journal of repetitive elements","volume":"16","author":"Jurka","year":"2000","journal-title":"Trends Genet."},{"key":"2023012408310121100_b16","first-page":"218","article-title":"UTR reconstruction and analysis using genomically aligned EST sequences","volume":"8","author":"Kan","year":"2000","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol."},{"key":"2023012408310121100_b17","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1101\/gr.155001","article-title":"Gene structure prediction and alternative splicing analysis using genomically aligned ESTs","volume":"11","author":"Kan","year":"2001","journal-title":"Genome Res."},{"key":"2023012408310121100_b18","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":"Karlin","year":"1990","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408310121100_b19","first-page":"656","article-title":"BLAT\u2014the BLAST-like alignment tool","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"2023012408310121100_b20","doi-asserted-by":"crossref","first-page":"reviews0008","DOI":"10.1186\/gb-2002-3-11-reviews0008","article-title":"Finding signals that regulate alternative splicing in the post-genomic era","volume":"3","author":"Ladd","year":"2002","journal-title":"Genome Biol."},{"key":"2023012408310121100_b21","doi-asserted-by":"crossref","first-page":"9407","DOI":"10.1073\/pnas.95.16.9407","article-title":"Evolutionary parameters of the transcribed mammalian genome: an analysis of 2,820 orthologous rodent and human sequences","volume":"95","author":"Makalowski","year":"1998","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408310121100_b22","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/70570","article-title":"A general approach to single-nucleotide polymorphism discovery","volume":"23","author":"Marth","year":"1999","journal-title":"Nat. Genet."},{"key":"2023012408310121100_b23","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1101\/gr.9.12.1288","article-title":"Frequent alternative splicing of human genes","volume":"9","author":"Mironov","year":"1999","journal-title":"Genome Res."},{"key":"2023012408310121100_b24","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1093\/nar\/29.13.2850","article-title":"Genome-wide detection of alternative splicing in expressed sequences of human genes","volume":"29","author":"Modrek","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023012408310121100_b25","first-page":"477","article-title":"EST_GENOME: a program to align spliced DNA sequences to unspliced genomic DNA","volume":"13","author":"Mott","year":"1997","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408310121100_b26","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0022-2836(70)90057-4","article-title":"A general method applicable to the search for similarities in the amino acid sequence of two proteins","volume":"48","author":"Needleman","year":"1970","journal-title":"J. Mol. Biol."},{"key":"2023012408310121100_b27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1101\/gr.9.2.167","article-title":"Mining SNPs from EST databases","volume":"9","author":"Picoult-Newberg","year":"1999","journal-title":"Genome Res."},{"key":"2023012408310121100_b28","volume-title":"Time Warps, String Edits, and Macromolecules: The Theory and Practice of Sequence Comparison","author":"Sankoff","year":"1983"},{"key":"2023012408310121100_b29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"A mathematical theory of communication","volume":"27","author":"Shannon","year":"1948","journal-title":"Bell Syst. Tech. J."},{"key":"2023012408310121100_b30","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":"Smith","year":"1981","journal-title":"J. Mol. Biol."},{"key":"2023012408310121100_b31","volume-title":"Biometry","author":"Sokal","year":"1995"},{"key":"2023012408310121100_b32","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1046-2023(05)80165-3","article-title":"Improved sensitivity of nucleic acid database searches using application-specific scoring matrices","volume":"3","author":"States","year":"1991","journal-title":"Methods"},{"key":"2023012408310121100_b33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev.bb.17.060188.001325","article-title":"Computer methods for analyzing sequence recognition of nucleic acids","volume":"17","author":"Stormo","year":"1988","journal-title":"Annu. Rev. Biophys. Biophys. Chem."},{"key":"2023012408310121100_b34","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1073\/pnas.86.4.1183","article-title":"Identifying protein-binding sites from unaligned DNA fragments","volume":"86","author":"Stormo","year":"1989","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408310121100_b35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/bioinformatics\/16.3.203","article-title":"Optimal spliced alignment of homologous cDNA to a genomic DNA template","volume":"16","author":"Usuka","year":"2000","journal-title":"Bioinformatics"},{"key":"2023012408310121100_b36","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1101\/gr.677503","article-title":"Computational discovery of internal micro-exons","volume":"13","author":"Volfovsky","year":"2003","journal-title":"Genome Res."},{"key":"2023012408310121100_b37","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1101\/gr.195301","article-title":"Spidey: a tool for mRNA-to-genomic alignments","volume":"11","author":"Wheelan","year":"2001","journal-title":"Genome Res."},{"key":"2023012408310121100_b38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0076-6879(96)66035-2","article-title":"Analysis of compositionally biased regions in sequence databases","volume":"266","author":"Wootton","year":"1996","journal-title":"Methods Enzymol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/1\/13\/48838607\/bioinformatics_22_1_13.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/1\/13\/48838607\/bioinformatics_22_1_13.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T08:38:33Z","timestamp":1674549513000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/1\/13\/219045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,2]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bti748","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2006,1,1]]},"published":{"date-parts":[[2005,11,2]]}}}