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PMID: 12843395 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Inferring genetic networks and identifying compound mode of action via expression profiling.

Science (New York, N.Y.) ·Vol. 301 ·No. 5629 ·2003-07-04 ·Pages 102-5

Gardner TS, di Bernardo D, Lorenz D, Collins JJ

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.

MeSH Terms
Algorithms Computational Biology DNA Damage DNA, Bacterial/genetics,metabolism Escherichia coli/genetics,metabolism Escherichia coli Proteins/metabolism Gene Expression Profiling Genes, Bacterial Genes, Regulator Linear Models Mathematics Mitomycin/pharmacology Models, Genetic Polymerase Chain Reaction RNA, Bacterial/genetics,metabolism RNA, Messenger/genetics,metabolism SOS Response, Genetics Transcription, Genetic
Chemicals
DNA, Bacterial Escherichia coli Proteins RNA, Bacterial RNA, Messenger Mitomycin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gardner Timothy S
Center for BioDynamics and Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
di Bernardo Diego
Lorenz David
Collins James J
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2003-07-04
Pages
102-5
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
Telethon · TGM03P17 · Italy
Telethon · TGM06S01 · Italy
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