Reverse engineering gene networks: Integrating genetic perturbations with dynamical modeling

Jesper Tegner*, M. K.Stephen Yeung, Jeff Hasty, James J. Collins

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

325 Scopus citations

Abstract

While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds.

Original languageEnglish (US)
Pages (from-to)5944-5949
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number10
DOIs
StatePublished - May 13 2003

ASJC Scopus subject areas

  • General

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