A new study from Jason Papin’s group at the University of Virginia’s Department of Biomedical Engineering published in Nature Communications describes the first genome-scale reconstruction (GENRE) of rat (iRno) and human (iHsa) metabolism. Their GENRE’s comprehensively map the metabolic differences between the species, such as their vitamin C and bile acid synthesis pathways.
Given that rats are used as human surrogate models to test hepatotoxicity in pre-clinical testing in pharma, understanding and predicting species-specific differences and similarities in drug metabolism between them and humans has cost, time and health benefits for drug development.
The authors integrated toxicogenomics microarray data from rat and human hepatocytes into their GENRE models as transcriptionally inferred metabolic biomarker responses (TIMBR).
They then ‘validated their predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans.’ (Blais et al. 2017)
Their study provides a systems-level overview of species-specific differences between rat and human metabolism captured with their in silico GENREs. This work highlights both the genomic similarities between humans and rats, but also reveals the metabolic pathway differences between the species which have been overlooked. This extra knowledge will aid preclinical development.
Written by Adam Tozer, Ph.D, Science Writer for www.TechnologyNetworks.com
Blais, E.M., Rawls, K.D., Dougherty, B.V., Li, Z.I., Kolling, G.L., Ye, P., Wallqvist, A. and Papin, J.A. (2017) ‘Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions’, Nature Communications, 8, p. 14250. doi: 10.1038/ncomms14250.