Genomic Promoter Analysis Predicts Functional Transcription Factor Binding

• Type of Material: Article
• Authors: J. Sunil Rao, Case Western Reserve University; Suresh Karanam, Emory University; Colleen D. McCabe, Emory University; Carlos S Moreno, Emory University
• Language: English
• Date: 2008-10-30
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2008 J. Sunil Rao et al
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.hindawi.com/journals/abi/2008/369830/
• Title of Journal or Parent Work: Advances in Bioinformatics
• ISSN: 1687-8027
• Volume: 2008
• Grant/Funding Information: This research was supported in part by NIH Grants K22-CA96560 and R01-CA106826 to CSM and NIH K25-CA89868 and NSF DMS-0405072 to JSR.; CDM was supported by DOD CDMRP Prostate Cancer Postdoctoral Training Fellowship PC060114.
• Research Categories: Biology, Bioinformatics; Biology, Genetics

Abstract

Background. The computational identification of functional transcription factor binding sites (TFBSs) remains a major challenge of computational biology. Results. We have analyzed the conserved promoter sequences for the complete set of human RefSeq genes using our conserved transcription factor binding site (CONFAC) software. CONFAC identified 16296 human-mouse ortholog gene pairs, and of those pairs, 9107 genes contained conserved TFBS in the 3 kb proximal promoter and first intron. To attempt to predict in vivo occupancy of transcription factor binding sites, we developed a novel marginal effect isolator algorithm that builds upon Bayesian methods for multigroup TFBS filtering and predicted the in vivo occupancy of two transcription factors with an overall accuracy of 84%. Conclusion. Our analyses show that integration of chromatin immunoprecipitation data with conserved TFBS analysis can be used to generate accurate predictions of functional TFBS. They also show that TFBS cooccurrence can be used to predict transcription factor binding to promoters in vivo.