Accession Number:

AD1089853

Title:

Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes

Descriptive Note:

Journal Article - Open Access

Corporate Author:

BIOTECHNOLOGY HPC SOFTWARE APPLICATIONS INST FORT DETRICK MD FORT DETRICK United States

Personal Author(s):

• Wallqvist,Anders
• Rawls,Kristopher D.
• Blais,Edik M.
• Dougherty,Bonnie V.
• Vinnakota,Kalyan C.
• Pannala,Venkat R.
• Kolling,Glynis L.
• Papin,Jason A.

Report Date:

2019-09-10

Pagination or Media Count:

41.0

Abstract:

Context-specific Genome-scale Metabolic Network Reconstructions GENREs provide a 1 means to understand cellular metabolism at a deeper level of physiological detail. Here, 2 we use transcriptomics data from chemically exposed rat hepatocytes to constrain a 3 GENRE of rat hepatocyte metabolism and predict biomarkers of liver toxicity using the 4 Transcriptionally Inferred Metabolic Biomarker Response TIMBR algorithm. We profiled 5 alterations in cellular hepatocyte metabolism following in vitro exposure to four toxicants 6 acetaminophen, carbon tetrachloride, 2,3,7,8-tetrachlorodibenzodioxin, and 7 trichloroethylene for six hours. TIMBR predictions were compared with paired fresh and 8 spent media metabolomics data from the same exposure conditions.

Descriptors:

• metabolism
• toxicology
• metabolomics
• genomes
• cells(biology)
• biological markers
• algorithms

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE