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A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.

Lang Li·Alfred S L Cheng·Victor X Jin·Henry H Paik·Meiyun Fan·Xiaoman Li·Wei Zhang·Jason Robarge·Curtis Balch·Ramana V Davuluri·Sun Kim·Tim H-M Huang·Kenneth P Nephew
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Abstract

MOTIVATION: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 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. AVAILABILITY: The software is available on request from the authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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AlgorithmsBase PairingBase SequenceBinding SitesComputer SimulationDiscriminant AnalysisEstrogen Receptor alphaGene Expression RegulationModels, ChemicalModels, GeneticModels, MolecularModels, StatisticalMolecular Sequence DataPromoter Regions, GeneticProtein BindingSequence AlignmentSequence Analysis, DNATranscription FactorsJournal ArticleResearch Support, N.I.H., Extramural

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Lang Li, Alfred S L Cheng, Victor X Jin, Henry H Paik, Meiyun Fan, Xiaoman Li, Wei Zhang, Jason Robarge, Curtis Balch, Ramana V Davuluri, Sun Kim, Tim H-M Huang, Kenneth P Nephew. 2006-06-29. A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.. https://doi.org/10.1093/bioinformatics%2Fbtl329

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