title: Reverse engineering and analysis of genome-wide gene regulatory networks from gene expression profiles using high-performance computing.
abstract: Regulation of gene expression is a carefully regulated phenomenon in the cell. “Reverse-engineering” algorithms try to reconstruct the regulatory interactions among genes from genome-scale measurements of gene expression profiles (microarrays). Mammalian cells express tens of thousands of genes; hence, hundreds of gene expression profiles are necessary in order to have acceptable statistical evidence of interactions between genes. As the number of profiles to be analyzed increases, so do computational costs and memory requirements. In this work, we designed and developed a parallel computing algorithm to reverse-engineer genome-scale gene regulatory networks from thousands of gene expression profiles. The algorithm is based on computing pairwise Mutual Information between each gene-pair. We successfully tested it to reverse engineer the Mus Musculus (mouse) gene regulatory network in liver from gene expression profiles collected from a public repository. A parallel hierarchical clustering algorithm was implemented to discover “communities” within the gene network. Network communities are enriched for genes involved in the same biological functions. The inferred network was used to identify two mitochondrial proteins.
authors.affiliation: Telethon Institute of Genetics and Medicine-TIGEM, Via P. Castellino 111, Naples 80131, Italy. belcastro@tigem.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Belcastro
authors.forename: Francesco
authors.initials: F
authors.lastname: Gregoretti
authors.forename: Velia
authors.initials: V
authors.lastname: Siciliano
authors.forename: Michele
authors.initials: M
authors.lastname: Santoro
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Angelo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Oliva
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
mesh_terms: D000465:Algorithms; D000818:Animals; D003205:Computing Methodologies; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D016678:Genome; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger