title: Inferring genetic networks and identifying compound mode of action via expression profiling.
abstract: The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.
authors.affiliation: Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Gardner
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
authors.forename: David
authors.initials: D
authors.lastname: Lorenz
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D004249:DNA Damage; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D005809:Genes, Regulator; D016014:Linear Models; D008433:Mathematics; D016685:Mitomycin / Q000494:pharmacology; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013014:SOS Response, Genetics; D014158:Transcription, Genetic
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D016685:Mitomycin