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
