Integrated genomic and proteomic analyses of a systematically perturbed metabolic network

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 messen ger RNAs responding to 20 systematic perturbations of the yeast galactose-u tilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physica l interactions governing the cellular response to each perturbation. We ref ine the model through further iterations of perturbation and global measure ments, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pat hways.