{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:07:41Z","timestamp":1760954861328},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-\u03b1 (ER\u03b1), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs.<\/jats:p>\n               <jats:p>Results: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ER\u03b1 target promoters (P-value &amp;lt; 0.001). The up-regulated targets significantly (P-value &amp;lt; 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC\/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ER\u03b1 target genes significantly (P-value &amp;lt; 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods.<\/jats:p>\n               <jats:p>Availability: The software is available on request from the authors.<\/jats:p>\n               <jats:p>Contact: lali@iupui.edu<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl329","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T14:27:07Z","timestamp":1151677627000},"page":"2210-2216","source":"Crossref","is-referenced-by-count":13,"title":["A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-\u03b1"],"prefix":"10.1093","volume":"22","author":[{"given":"Lang","family":"Li","sequence":"first","affiliation":[{"name":"Division of Biostatistics, Department of Medicine, Indiana University School of Medicine 1 \u00a0 1 \u00a0 \u00a0 Indianapolis, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred S. L.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University 2 \u00a0 2 \u00a0 \u00a0 Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor X.","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University 2 \u00a0 2 \u00a0 \u00a0 Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry H.","family":"Paik","sequence":"additional","affiliation":[{"name":"Medical Sciences, Indiana University School of Medicine 3 \u00a0 3 \u00a0 \u00a0 Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiyun","family":"Fan","sequence":"additional","affiliation":[{"name":"Medical Sciences, Indiana University School of Medicine 3 \u00a0 3 \u00a0 \u00a0 Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoman","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Medicine, Indiana University School of Medicine 1 \u00a0 1 \u00a0 \u00a0 Indianapolis, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Medicine, Indiana University School of Medicine 1 \u00a0 1 \u00a0 \u00a0 Indianapolis, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Robarge","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Medicine, Indiana University School of Medicine 1 \u00a0 1 \u00a0 \u00a0 Indianapolis, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis","family":"Balch","sequence":"additional","affiliation":[{"name":"Medical Sciences, Indiana University School of Medicine 3 \u00a0 3 \u00a0 \u00a0 Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramana V.","family":"Davuluri","sequence":"additional","affiliation":[{"name":"Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University 2 \u00a0 2 \u00a0 \u00a0 Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Sciences, Indiana University School of Medicine 3 \u00a0 3 \u00a0 \u00a0 Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim H.-M.","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University 2 \u00a0 2 \u00a0 \u00a0 Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth P.","family":"Nephew","sequence":"additional","affiliation":[{"name":"Medical Sciences, Indiana University School of Medicine 3 \u00a0 3 \u00a0 \u00a0 Bloomington, IN 47405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,6,29]]},"reference":[{"key":"2023012409210715600_b1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/bioinformatics\/14.1.48","article-title":"Combining evidence using P-value: application to sequence homology search","volume":"14","author":"Bailey","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012409210715600_b2","doi-asserted-by":"crossref","first-page":"ii16","DOI":"10.1093\/bioinformatics\/btg1054","article-title":"Searching for statistically significant regulatory modules","volume":"19","author":"Bailey","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012409210715600_b3","first-page":"28","article-title":"Fitting a mixture model by expectation maximization to discover motifs in biopolymer","author":"Bailey","year":"1994"},{"key":"2023012409210715600_b4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1073\/pnas.231608898","article-title":"Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome","volume":"99","author":"Berman","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012409210715600_b5","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/00000658-199506000-00010","article-title":"Oncogene protein co-expression. Value of Ha-ras, c-myc, c-fos, and p53 as prognostic discriminants for breast carcinoma","volume":"221","author":"Bland","year":"1995","journal-title":"Ann. Surg."},{"key":"2023012409210715600_b6","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/84792","article-title":"Regulatory element detection using correlation with expression","volume":"27","author":"Bussemaker","year":"2001","journal-title":"Nat. Genet."},{"key":"2023012409210715600_b7","article-title":"Classification Regression Trees","author":"Breiman","year":"1984"},{"key":"2023012409210715600_b8","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2005.12.016","article-title":"Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor a-responsive promoters","volume":"21","author":"Cheng","year":"2006","journal-title":"Mole. Cell"},{"key":"2023012409210715600_b9","first-page":"521","article-title":"Initial sequencing and comparative analysis of the mouse genome","volume":"420","author":"Consortium","year":"2002","journal-title":"Nature"},{"key":"2023012409210715600_b10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1006\/jmbi.1997.0965","article-title":"A statistical model for locating regulatory regions in genomic DNA","volume":"268","author":"Crowley","year":"1997","journal-title":"J. Mol. Biol."},{"key":"2023012409210715600_b11","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/bioinformatics\/17.10.878","article-title":"Detection of cis-element clusters in higher eukaryotic DNA","volume":"17","author":"Firth","year":"2001","journal-title":"Bioinformatics"},{"key":"2023012409210715600_b12","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1093\/nar\/gkf438","article-title":"Statistical significance of clusters of motifs represented by position specific scoring matrices in nucleotide sequences","volume":"30","author":"Firth","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012409210715600_b13","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1006\/jmbi.1997.1140","article-title":"A novel method to develop highly specific models for regulatory units detects a new LTR in GenBank which contains a functional promoter","volume":"270","author":"Frech","year":"1997","journal-title":"J. Mol. Biol."},{"key":"2023012409210715600_b14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2005.03.007","article-title":"The role of DNA response elements as allosteric modulators of steroid receptor function","volume":"236","author":"Geserick","year":"2005","journal-title":"Mol. Cell Endocrinol."},{"key":"2023012409210715600_b15","doi-asserted-by":"crossref","first-page":"16566","DOI":"10.1016\/S0021-9258(19)89426-7","article-title":"Repression of AP-1-stimulated transcription by c-Ets-1","volume":"269","author":"Goldberg","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2023012409210715600_b16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1198\/016214503388619094","article-title":"Discovery of conserved sequence patterns using a stochastic dictionary model","volume":"98","author":"Gupta","year":"2003","journal-title":"J. Am. Stat. Assoc."},{"key":"2023012409210715600_b17","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1093\/nar\/gkh1005","article-title":"Identifying estrogen receptor alpha target genes using integrated computational genomics and chromatin immunoprecipitation microarray","volume":"32","author":"Jin","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012409210715600_b18","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/bioinformatics\/bth333","article-title":"Regulatory motif finding by logic regression","volume":"20","author":"Keles","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012409210715600_b19","first-page":"477","article-title":"Eukrayotic promoter recognition by binding sites for transcription factors","volume":"11","author":"Kondrakhin","year":"1995","journal-title":"Comp. Appl. Biosci."},{"key":"2023012409210715600_b20","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1101\/gr.180601","article-title":"A predictive model for regulatory sequences directing liver-specific transcription","volume":"11","author":"Krivan","year":"2001","journal-title":"Genome Res."},{"key":"2023012409210715600_b21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2004.02.021","article-title":"About GATA3, HNF3A, and XBP1, three genes co-expressed with the oestrogen receptor-alpha gene (ESR1) in breast cancer","volume":"219","author":"Lacroix","year":"2004","journal-title":"Mol. Cell Endocrinol."},{"key":"2023012409210715600_b22","doi-asserted-by":"crossref","first-page":"R66","DOI":"10.1186\/gb-2004-5-9-r66","article-title":"Discovery of estrogen receptor \u03b1 target genes and response elements in breast tumor cells","volume":"5","author":"Lin","year":"2004","journal-title":"Genome Biol."},{"key":"2023012409210715600_b23","doi-asserted-by":"crossref","first-page":"506","DOI":"10.2741\/1546","article-title":"The transcription factor Ets-1 in breast cancer","volume":"10","author":"Lincoln","year":"2005","journal-title":"Front Biosci."},{"key":"2023012409210715600_b24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1022904624054","article-title":"Estrogen-induced Ets-1 promotes capillary formation in an in vitro tumor angiogenesis model","volume":"78","author":"Lincoln","year":"2003","journal-title":"Breast Cancer Res. Treat."},{"key":"2023012409210715600_b25","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1080\/01621459.1995.10476622","volume":"90","author":"Liu","year":"1995","journal-title":"J. Am. Stat. Assoc."},{"key":"2023012409210715600_b26","first-page":"127","article-title":"BioProspector: discovering conserved DNA motifs in upstream regulatory regions of co-expressed genes","author":"Liu","year":"2001","journal-title":"Pac. Symp. 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Cancer Res."},{"key":"2023012409210715600_b30","doi-asserted-by":"crossref","first-page":"865s","DOI":"10.1158\/1078-0432.865s.11.2","article-title":"Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer","volume":"11","author":"Osborne","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"2023012409210715600_b31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nrc904","article-title":"c-MYC: more than just a matter of life and death","volume":"2","author":"Pelengaris","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"2023012409210715600_b32","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1006\/jmbi.1995.0349","article-title":"Predicting Pol II promoter sequences using transcription factor binding sites","volume":"249","author":"Prestridge","year":"1995","journal-title":"J. Mol. Biol."},{"key":"2023012409210715600_b33","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511812651","volume-title":"Pattern recognition and neural network","author":"Ripley","year":"1996"},{"key":"2023012409210715600_b34","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.1128\/MCB.25.17.7917-7925.2005","article-title":"Survival signals generated by estrogen and phospholipase D in MCF-7 breast cancer cells are dependent on Myc","volume":"25","author":"Rodrik","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"2023012409210715600_b35","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1101\/gad.1272505","article-title":"Active chromatin domains are defined by acetylation islands revealed by genome-wide mapping","volume":"19","author":"Roh","year":"2005","journal-title":"Genes Dev."},{"key":"2023012409210715600_b36","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nbt1098-939","article-title":"Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation","volume":"16","author":"Roth","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"2023012409210715600_b37","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1198\/1061860032238","article-title":"Logic Regression","volume":"12","author":"Ruczinski","year":"2003","journal-title":"J. Comput. Graphical Stat."},{"key":"2023012409210715600_b38","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/sj.onc.1206131","article-title":"Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins","volume":"22","author":"Rushton","year":"2003","journal-title":"Oncogene"},{"key":"2023012409210715600_b39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/bcr1287","article-title":"Endocrinology and hormone therapy in breast cancer: new insight into estrogen receptor-alpha function and its implication for endocrine therapy resistance in breast cancer","volume":"7","author":"Schiff","year":"2005","journal-title":"Breast Cancer Res."},{"key":"2023012409210715600_b40","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1016\/j.ejca.2005.08.013","article-title":"ETS transcritpion factors and their emerging roles in human cancer","volume":"41","author":"Seth","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"2023012409210715600_b41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/bioinformatics\/btg1040","article-title":"A probabilistic method to detect regulatory modules","volume":"19","author":"Sinha","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012409210715600_b42","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"Clustal W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalities and weight matrix choice","volume":"22","author":"Thompson","year":"1994","journal-title":"Nucleic Acids Res."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/18\/2210\/48841363\/bioinformatics_22_18_2210.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/18\/2210\/48841363\/bioinformatics_22_18_2210.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T09:59:51Z","timestamp":1674554391000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/18\/2210\/316481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,29]]},"references-count":42,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2006,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btl329","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2006,9,15]]},"published":{"date-parts":[[2006,6,29]]}}}