Network-based prediction of human tissue-specific metabolism.

TitleNetwork-based prediction of human tissue-specific metabolism.
Publication TypeJournal Article
Year of Publication2008
AuthorsShlomi T, Cabili MN, Herrgård MJ, Palsson BØ, Ruppin E
JournalNat Biotechnol
Date Published2008 Sep
KeywordsCell Physiological Phenomena, Computational Biology, Databases, Protein, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, Humans, Metabolic Networks and Pathways, Models, Genetic, Models, Statistical, Reproducibility of Results, Software

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.

PubMed URL
Alternate TitleNat. Biotechnol.
PubMed ID18711341