title: Unraveling networks of co-regulated genes on the sole basis of genome sequences.
abstract: With the growing number of available microbial genome sequences, regulatory signals can now be revealed as conserved motifs in promoters of orthologous genes (phylogenetic footprints). A next challenge is to unravel genome-scale regulatory networks. Using as sole input genome sequences, we predicted cis-regulatory elements for each gene of the yeast Saccharomyces cerevisiae by discovering over-represented motifs in the promoters of their orthologs in 19 Saccharomycetes species. We then linked all genes displaying similar motifs in their promoter regions and inferred a co-regulation network including 56,919 links between 3171 genes. Comparison with annotated regulons highlights the high predictive value of the method: a majority of the top-scoring predictions correspond to already known co-regulations. We also show that this inferred network is as accurate as a co-expression network built from hundreds of transcriptome microarray experiments. Furthermore, we experimentally validated 14 among 16 new functional links between orphan genes and known regulons. This approach can be readily applied to unravel gene regulatory networks from hundreds of microbial genomes for which no other information is available except the sequence. Long-term benefits can easily be perceived when considering the exponential increase of new genome sequences.
authors.affiliation: Lab. Bioinformatique des Génomes et des Réseaux (BiGRe), Université Libre de Bruxelles (ULB), CP 263, Campus Plaine, Bld du Triomphe, 1050 Brussels, Belgium.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brohée
authors.forename: Rekin's
authors.initials: R
authors.lastname: Janky
authors.forename: Fadi
authors.initials: F
authors.lastname: Abdel-Sater
authors.forename: Gilles
authors.initials: G
authors.lastname: Vanderstocken
authors.forename: Bruno
authors.initials: B
authors.lastname: André
authors.forename: Jacques
authors.initials: J
authors.lastname: van Helden
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D018085:Regulon; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors