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Science 4 July 2003:
Vol. 301. no. 5629, pp. 102 - 105
DOI: 10.1126/science.1081900
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Reports

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

Timothy S. Gardner,1* Diego di Bernardo,1,2* David Lorenz,1 James J. Collins1{dagger}

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.

1 Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA. 2 Telethon Institute for Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131, Naples, Italy.


* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jcollins{at}bu.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)