title: oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes.
abstract: Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective. Creation of a system for the efficient identification of common regulatory mechanisms in a subset of co-expressed human genes promises to break a roadblock in functional genomics research. We have developed an integrated system that searches for evidence of co-regulation by one or more transcription factors (TFs). oPOSSUM combines a pre-computed database of conserved TFBSs in human and mouse promoters with statistical methods for identification of sites over-represented in a set of co-expressed genes. The algorithm successfully identified mediating TFs in control sets of tissue-specific genes and in sets of co-expressed genes from three transcript profiling studies. Simulation studies indicate that oPOSSUM produces few false positives using empirically defined thresholds and can tolerate up to 50% noise in a set of co-expressed genes.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia Vancouver, BC, Canada.
authors.forename: Shannan J
authors.initials: SJ
authors.lastname: Ho Sui
authors.forename: James R
authors.initials: JR
authors.lastname: Mortimer
authors.forename: David J
authors.initials: DJ
authors.lastname: Arenillas
authors.forename: Jochen
authors.initials: J
authors.lastname: Brumm
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Walsh
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kennedy
authors.forename: Wyeth W
authors.initials: WW
authors.lastname: Wasserman
mesh_terms: D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D030561:Databases, Nucleic Acid; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020407:Internet; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors