Title | Network-based prediction of human tissue-specific metabolism. |
Year of Publication | 2008 |
Authors | T. Shlomi; M.N. Cabili; M.J. Herrgard; B.Ø. Palsson; E. Ruppin |
Journal | PLoS Comput Biol |
Abstract | 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. |
URL | PubMed |