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

Edik M. Blais, Kristopher D. Rawls, Bonnie V. Dougherty, Zhuo I. Li, Glynis L. Kolling, Ping Ye, Anders Wallqvist and Jason A. Papin ()
Additional contact information
Edik M. Blais: University of Virginia
Kristopher D. Rawls: University of Virginia
Bonnie V. Dougherty: University of Virginia
Zhuo I. Li: University of Virginia
Glynis L. Kolling: University of Virginia
Ping Ye: Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command
Anders Wallqvist: Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command
Jason A. Papin: University of Virginia

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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 mechanistic insights into species-specific metabolism and facilitate the selection of biomarkers consistent with rat and human biology. These models can serve as powerful computational platforms for contextualizing experimental data and making functional predictions for clinical and basic science applications.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms14250 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14250

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14250

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().