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Science 4 May 2001:
Vol. 292. no. 5518, pp. 929 - 934
DOI: 10.1126/science.292.5518.929
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Reports

Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network

Trey Ideker,12* Vesteinn Thorsson,12 Jeffrey A. Ranish,12 Rowan Christmas,1 Jeremy Buhler,3 Jimmy K. Eng,1 Roger Bumgarner,4 David R. Goodlett,1 Ruedi Aebersold,12 Leroy Hood12

We demonstrate an integrated approach to build, test, and refine a model of a cellular pathway, in which perturbations to critical pathway components are analyzed using DNA microarrays, quantitative proteomics, and databases of known physical interactions. Using this approach, we identify 997 messenger RNAs responding to 20 systematic perturbations of the yeast galactose-utilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physical interactions governing the cellular response to each perturbation. We refine the model through further iterations of perturbation and global measurements, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pathways.

1 The Institute for Systems Biology, 4225 Roosevelt Way NE, Suite 200, Seattle, WA 98105, USA. Departments of
2 Molecular Biotechnology,
3 Computer Science, and
4 Microbiology, University of Washington, Seattle, WA 98195, USA.
*   To whom correspondence should be addressed at The Institute for Systems Biology. E-mail: tideker{at}systemsbiology.org

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