{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:14:30Z","timestamp":1787008470281,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: A key goal in molecular biology is to understand the mechanisms by which a cell regulates the transcription of its genes. One important aspect of this transcriptional regulation is the binding of transcription factors (TFs) to their specific cis-regulatory counterparts on the DNA. TFs recognize and bind their DNA counterparts according to the structure of their DNA-binding domains (e.g. zinc finger, leucine zipper, homeodomain). The structure of these domains can be used as a basis for grouping TFs into classes. Although the structure of DNA-binding domains varies widely across TFs generally, the TFs within a particular class bind to DNA in a similar fashion, suggesting the existence of class-specific features in the DNA sequences bound by each class of TFs.<\/jats:p>\n                  <jats:p>Results: In this paper, we apply a sparse Bayesian learning algorithm to identify a small set of class-specific features in the DNA sequences bound by different classes of TFs; the algorithm simultaneously learns a true multi-class classifier that uses these features to predict the DNA-binding domain of the TF that recognizes a particular set of DNA sequences. We train our algorithm on the six largest classes in TRANSFAC, comprising a total of 587 TFs. We learn a six-class classifier for this training set that achieves 87% leave-one-out cross-validation accuracy. We also identify features within cis-regulatory sequences that are highly specific to each class of TF, which has significant implications for how TF binding sites should be modeled for the purpose of motif discovery.<\/jats:p>\n                  <jats:p>Contact: \u00a0lee@cs.duke.edu; amink@cs.duke.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti731","type":"journal-article","created":{"date-parts":[[2005,11,2]],"date-time":"2005-11-02T20:13:48Z","timestamp":1130962428000},"page":"157-163","source":"Crossref","is-referenced-by-count":26,"title":["Sequence features of DNA binding sites reveal structural class of associated transcription factor"],"prefix":"10.1093","volume":"22","author":[{"given":"Leelavati","family":"Narlikar","sequence":"first","affiliation":[{"name":"Duke University, Department of Computer Science \u00a0 Box 90129, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Hartemink","sequence":"additional","affiliation":[{"name":"Duke University, Department of Computer Science \u00a0 Box 90129, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,11,2]]},"reference":[{"key":"2023012408304118900_b1","first-page":"2","article-title":"Detecting non-adjoining correlations within signals in DNA","author":"Agarwal","year":"1998"},{"key":"2023012408304118900_b2","article-title":"Developmental expression of transcription factors","volume-title":"Academic Dissertation","author":"Aitola","year":"2002"},{"key":"2023012408304118900_b3","volume-title":"Molecular Biology of the Cell","author":"Alberts","year":"2002","edition":"4th edn"},{"key":"2023012408304118900_b4","doi-asserted-by":"crossref","first-page":"5172","DOI":"10.1073\/pnas.94.10.5172","article-title":"A natural classification of the basic helix loop helix class of transcription factors","volume":"94","author":"Atchley","year":"1997","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408304118900_b5","first-page":"28","article-title":"Fitting a mixture model by expectation maximization to discover motifs in biopolymers","volume-title":"ISMB '94","author":"Bailey","year":"1994"},{"key":"2023012408304118900_b6","first-page":"28","article-title":"Modeling dependencies in protein-DNA binding sites","author":"Barash","year":"2003"},{"key":"2023012408304118900_b7","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1093\/nar\/30.5.1255","article-title":"Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors","volume":"30","author":"Bulyk","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012408304118900_b8","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/S0006-3495(00)76324-7","article-title":"Bending and adaptability to proteins of the cAMP DNA-responsive element: molecular dynamics contrasted with NMR","volume":"79","author":"Derreumaux","year":"2000","journal-title":"Biophys. J."},{"key":"2023012408304118900_b9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature02800","article-title":"Transcriptional regulatory code of a eukaryotic genome","volume":"431","author":"Harbison","year":"2004","journal-title":"Nature"},{"key":"2023012408304118900_b10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1093\/bioinformatics\/15.7.563","article-title":"Identifying DNA and protein patterns with statistically significant alignments of multiple sequences","volume":"15","author":"Hertz","year":"1999","journal-title":"Bioinformatics"},{"key":"2023012408304118900_b11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature01644","article-title":"Sequencing and comparison of yeast species to identify genes and regulatory elements","volume":"432","author":"Kellis","year":"2003","journal-title":"Nature"},{"key":"2023012408304118900_b12","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1109\/TPAMI.2005.127","article-title":"Learning sparse Bayesian classifiers: multi-class formulation, fast algorithms, and generalization bounds","volume":"27","author":"Krishnapuram","year":"2005","journal-title":"IEEE Trans. Pattern Anal. Machine Intell."},{"key":"2023012408304118900_b13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/31860","article-title":"Allosteric effects of DNA on transcriptional regulators","volume":"392","author":"Lefstin","year":"1998","journal-title":"Nature"},{"key":"2023012408304118900_b14","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1080\/01621459.1994.10476829","article-title":"The collapsed Gibbs sampler with applications to a gene regulation problem","volume":"89","author":"Liu","year":"1994","journal-title":"J. Amer. Stat. Assoc."},{"key":"2023012408304118900_b15","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nbt717","article-title":"An algorithm for finding protein-DNA binding sites with applications to chromatin immunoprecipitation microarray experiments","volume":"20","author":"Liu","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"2023012408304118900_b16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1093\/nar\/gkg046","article-title":"The InterPro Database: 2003 brings increased coverage and new features","volume":"31","author":"Mulder","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2023012408304118900_b17","article-title":"Informative priors improve motif discovery","author":"Narlikar","year":"2005"},{"key":"2023012408304118900_b18","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1146\/annurev.bi.61.070192.005201","article-title":"Transcription factors: structural families and principles of DNA recognition","volume":"61","author":"Pabo","year":"1992","journal-title":"Annu. Rev. Biochem."},{"key":"2023012408304118900_b19","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nbt1098-939","article-title":"Finding DNA regulatory motifs within unaligned non-coding sequences clustered by whole-genome mRNA quantitation","volume":"16","author":"Roth","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"2023012408304118900_b20","doi-asserted-by":"crossref","first-page":"D91","DOI":"10.1093\/nar\/gkh012","article-title":"JASPAR: an open access database for eukaryotic transcription factor binding profiles","volume":"32","author":"Sandelin","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012408304118900_b21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jmb.2004.02.048","article-title":"Constrained binding site diversity within families of transcription factors enhances pattern discovery bioinformatics","volume":"338","author":"Sandelin","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2023012408304118900_b22","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/nar\/12.1Part2.505","article-title":"Computer methods to locate signals in nucleic acid sequences","volume":"12","author":"Staden","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"2023012408304118900_b23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1162\/neco.1995.7.1.117","article-title":"Bayesian regularization and pruning using a Laplace prior","volume":"7","author":"Williams","year":"1995","journal-title":"Neural Comput."},{"key":"2023012408304118900_b24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/nar\/29.1.281","article-title":"The TRANSFAC system on gene expression regulation","volume":"29","author":"Wingender","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023012408304118900_b25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1146\/annurev.biophys.29.1.183","article-title":"DNA recognition by Cys2His2 zinc finger proteins","volume":"3","author":"Wolfe","year":"2000","journal-title":"Annu. Rev. Biomol. Struct."},{"key":"2023012408304118900_b26","doi-asserted-by":"crossref","first-page":"10523","DOI":"10.1073\/pnas.0403564101","article-title":"MotifPrototyper: a Bayesian profile model for motif families","volume":"101","author":"Xing","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408304118900_b27","first-page":"499","article-title":"A weight array method for splicing signal analysis","volume":"9","author":"Zhang","year":"1993","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408304118900_b28","first-page":"389","article-title":"Structural determinants of DNA-binding specificity by steroid receptors","volume":"9","author":"Zilliacus","year":"1995","journal-title":"Mol. Endocrinol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/2\/157\/48838397\/bioinformatics_22_2_157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/2\/157\/48838397\/bioinformatics_22_2_157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T03:36:57Z","timestamp":1674531417000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/2\/157\/421605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,2]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bti731","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2006,1,15]]},"published":{"date-parts":[[2005,11,2]]}}}