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Validation and refinement of gene-regulatory pathways on a network of physical interactions

Chen-Hsiang Yeang1, H Craig Mak2, Scott McCuine2, Christopher Workman2, Tommi Jaakkola3 and Trey Ideker2*

Author affiliations

1 Center for Biomolecular Science and Engineering, Baskin School of Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, USA

2 Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA

3 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

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Citation and License

Genome Biology 2005, 6:R62  doi:10.1186/gb-2005-6-7-r62

Published: 1 July 2005

Abstract

As genome-scale measurements lead to increasingly complex models of gene regulation, systematic approaches are needed to validate and refine these models. Towards this goal, we describe an automated procedure for prioritizing genetic perturbations in order to discriminate optimally between alternative models of a gene-regulatory network. Using this procedure, we evaluate 38 candidate regulatory networks in yeast and perform four high-priority gene knockout experiments. The refined networks support previously unknown regulatory mechanisms downstream of SOK2 and SWI4.