U.S. Department of Energy

Pacific Northwest National Laboratory

In silico method for modelling metabolism and gene product expression at genome scale.

TitleIn silico method for modelling metabolism and gene product expression at genome scale.
Publication TypeJournal Article
Year of Publication2012
AuthorsLerman JA, Hyduke DR, Latif H, Portnoy VA, Lewis NE, Orth JD, Schrimpe-Rutledge AC, Smith RD, Adkins JN, Zengler K, Palsson BO
JournalNat Commun
KeywordsComputational Biology, Systems Biology, Thermotoga maritima, Transcriptome

Transcription and translation use raw materials and energy generated metabolically to create the macromolecular machinery responsible for all cellular functions, including metabolism. A biochemically accurate model of molecular biology and metabolism will facilitate comprehensive and quantitative computations of an organism's molecular constitution as a function of genetic and environmental parameters. Here we formulate a model of metabolism and macromolecular expression. Prototyping it using the simple microorganism Thermotoga maritima, we show our model accurately simulates variations in cellular composition and gene expression. Moreover, through in silico comparative transcriptomics, the model allows the discovery of new regulons and improving the genome and transcription unit annotations. Our method presents a framework for investigating molecular biology and cellular physiology in silico and may allow quantitative interpretation of multi-omics data sets in the context of an integrated biochemical description of an organism.

PubMed ID22760628
PubMed Central IDPMC3827721
Grant ListGM085764 / GM / NIGMS NIH HHS / United States
U01 GM102098 / GM / NIGMS NIH HHS / United States
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