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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Algorithms
-
Computational Biology*
-
DNA Damage
-
DNA, Bacterial / genetics
-
DNA, Bacterial / metabolism
-
Escherichia coli / genetics*
-
Escherichia coli / 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
-
RNA, Bacterial / metabolism
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
SOS Response, Genetics*
-
Transcription, Genetic
Substances
-
DNA, Bacterial
-
Escherichia coli Proteins
-
RNA, Bacterial
-
RNA, Messenger
-
Mitomycin