Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes
Journal Article - Open Access
BIOTECHNOLOGY HPC SOFTWARE APPLICATIONS INST FORT DETRICK MD FORT DETRICK United States
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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.
- Medicine and Medical Research