Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions.

ABSTRACT: The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs. We validate comparative predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans. Our results provide m

SUBMITTER: Blais EM 

PROVIDER: S-EPMC5309818 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature