Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Computational Biology
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Culture Media
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Databases, Factual
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Fungal Proteins / metabolism
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Galactose / metabolism*
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Galactosephosphates / metabolism
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Gene Expression Profiling*
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Gene Expression Regulation, Fungal
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Genome, Fungal*
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Models, Biological
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Models, Genetic
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Monosaccharide Transport Proteins / metabolism
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Mutation
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Oligonucleotide Array Sequence Analysis
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Proteome*
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RNA, Fungal / genetics
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RNA, Fungal / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
Substances
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Culture Media
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Fungal Proteins
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GAL2 protein, S cerevisiae
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Galactosephosphates
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Monosaccharide Transport Proteins
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Proteome
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RNA, Fungal
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RNA, Messenger
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Saccharomyces cerevisiae Proteins
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galactose-1-phosphate
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Galactose