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 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.
Ideker
T
T
The Institute for Systems Biology, 4225 Roosevelt Way NE, Suite 200, Seattle, WA 98105, USA. tideker@systemsbiology.org
Thorsson
V
V
Ranish
J A
JA
Christmas
R
R
Buhler
J
J
Eng
J K
JK
Bumgarner
R
R
Goodlett
D R
DR
Aebersold
R
R
Hood
L
L
D019295:Computational Biology; D003470:Culture Media; D016208:Databases, Factual; D005656:Fungal Proteins / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D005695:Galactosephosphates / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008954:Models, Biological; D008957:Models, Genetic; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D003470:Culture Media; D005656:Fungal Proteins; C106901:GAL2 protein, S cerevisiae; D005695:Galactosephosphates; D009004:Monosaccharide Transport Proteins; D020543:Proteome; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C029973:galactose-1-phosphate; D005690:Galactose