Journal
NATURE BIOTECHNOLOGY
Volume 26, Issue 9, Pages 1003-1010Publisher
NATURE RESEARCH
DOI: 10.1038/nbt.1487
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Funding
- National Institutes of Health [GM071808]
- Israeli Science Foundation
- German-Israeli Foundation
- Tauber fund
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM071808] Funding Source: NIH RePORTER
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Direct in vivo investigation of mammalian metabolism is complicated by the distinct metabolic functions of different tissues. We present a computational method that successfully describes the tissue specificity of human metabolism on a large scale. By integrating tissue-specific gene- and protein-expression data with an existing comprehensive reconstruction of the global human metabolic network, we predict tissue-specific metabolic activity in ten human tissues. This reveals a central role for post- transcriptional regulation in shaping tissue-specific metabolic activity profiles. The predicted tissue specificity of genes responsible for metabolic diseases and tissue-specific differences in metabolite exchange with biofluids extend markedly beyond tissue-specific differences manifest in enzyme-expression data, and are validated by large-scale mining of tissue-specificity data. Our results establish a computational basis for the genome-wide study of normal and abnormal human metabolism in a tissue-specific manner.
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