title: Coordinated concentration changes of transcripts and metabolites in Saccharomyces cerevisiae.
abstract: Metabolite concentrations can regulate gene expression, which can in turn regulate metabolic activity. The extent to which functionally related transcripts and metabolites show similar patterns of concentration changes, however, remains unestablished. We measure and analyze the metabolomic and transcriptional responses of Saccharomyces cerevisiae to carbon and nitrogen starvation. Our analysis demonstrates that transcripts and metabolites show coordinated response dynamics. Furthermore, metabolites and gene products whose concentration profiles are alike tend to participate in related biological processes. To identify specific, functionally related genes and metabolites, we develop an approach based on Bayesian integration of the joint metabolomic and transcriptomic data. This algorithm finds interactions by evaluating transcript-metabolite correlations in light of the experimental context in which they occur and the class of metabolite involved. It effectively predicts known enzymatic and regulatory relationships, including a gene-metabolite interaction central to the glycolytic-gluconeogenetic switch. This work provides quantitative evidence that functionally related metabolites and transcripts show coherent patterns of behavior on the genome scale and lays the groundwork for building gene-metabolite interaction networks directly from systems-level data.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Bradley
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Brauer
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D053898:Biosynthetic Pathways; D002244:Carbon / Q000378:metabolism; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005800:Genes, Fungal; D023281:Genomics / Q000379:methods*; D050261:Glycogenolysis; D006019:Glycolysis; D055432:Metabolomics / Q000379:methods*; D009584:Nitrogen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry; D014158:Transcription, Genetic
chemical_list: D002244:Carbon; D009584:Nitrogen