Inferring genetic networks and identifying compound mode of action via expression profiling.
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.
Gardner
Timothy S
TS
Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
di Bernardo
Diego
D
Lorenz
David
D
Collins
James J
JJ
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
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D016685:Mitomycin