title: Detection of coregulation in differential gene expression profiles.
abstract: Genomics and proteomics approaches generate distinct gene expression and protein profiles, listing individual genes embedded in broad functional terms as gene ontologies. However, interpretation of gene profiles in a regulatory and functional context remains a major issue. Elucidation of regulatory mechanisms at the gene expression level via analysis of promoter regions is a prominent procedure to decipher such gene regulatory networks. We propose a novel genetic algorithm (GA) to extract joint promoter modules in a set of coexpressed genes as resulting from differential gene expression experiments. Algorithm design has focused on the following constraints: (I) identification of the major promoter modules, which are (II) characterized by a maximum number of joint motifs and (III) are found in a maximum number of coexpressed genes. The capability of the GA in detecting multiple modules was evaluated on various test data sets, analyzing the impact of the number of motifs per promoter module, the number of genes associated with a module, as well as the total number of distinct promoter modules encoded in a sequence set. In addition to the test data sets, the GA was evaluated on two biological examples, namely a muscle-specific data set and the upstream sequences of the beta-actin gene (ACTB) derived from different species, complemented by a comparison to alternative promoter module identification routines.
authors.affiliation: Institute for Biomolecular Structural Chemistry, University of Vienna, Campus Vienna Biocenter 6, 1030 Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.forename: Alexander
authors.initials: A
authors.lastname: Kainz
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
authors.forename: Arno
authors.initials: A
authors.lastname: Lukas
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics; D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D023281:Genomics; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D040901:Proteomics; D049490:Systems Biology
chemical_list: D000199:Actins