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

Science, 4 July 2003
Vol. 301, Issue 5629, p. 102-105
DOI: 10.1126/science.1081900

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

  1. Timothy S. Gardner1,*,
  2. Diego di Bernardo1,2,*,
  3. David Lorenz1,
  4. James J. Collins1,
  1. 1Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA. 2Telethon Institute for Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131, Naples, Italy.
  1. To whom correspondence should be addressed. E-mail: jcollins{at}
  • * These authors contributed equally to this work.


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.

    • Received for publication 24 December 2002.
    • Accepted for publication 3 June 2003.


    T. S. Gardner, D. di Bernardo, D. Lorenz, and J. J. Collins, Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling. Science 301, 102-105 (2003).

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