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Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling

Science  04 Jul 2003:
Vol. 301, Issue 5629, pp. 102-105
DOI: 10.1126/science.1081900

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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.

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