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

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.

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Document Details

Document Type
Technical Report
Publication Date
Sep 10, 2019
Accession Number
AD1089853

Entities

People

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

Tags

DTIC Thesaurus Topics

  • Amines
  • Amino Acids
  • Cells
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Computational Biology
  • Computational Science
  • Gene Expression
  • Liquid Chromatography
  • Mass Spectrometry
  • Metabolism
  • Metabolomics
  • Organic Chemistry
  • Spectrometry
  • Stem Cells
  • Systems Biology

Fields of Study

  • Biology

Readers

  • Computational Linguistics
  • Oncology and Biomarker-Based Cancer Detection.
  • Toxicology/Environmental Toxicology

Technology Areas

  • AI & ML