ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 21 citations in OpenAlex.
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- Identifying metabolic adaptations characteristic of cardiotoxicity using paired transcriptomics and metabolomics data integrated with a computational model of heart metabolism.PLoS computational biology · 2024Article
- Transcriptome-based biomarker prediction for Parkinson's disease using genome-scale metabolic modeling.Scientific reports · 2024Article
- Metabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses.PLoS computational biology · 2023Article
- Loss of the Kidney Urate Transporter, Urat1, Leads to Disrupted Redox Homeostasis in Mice.Antioxidants (Basel, Switzerland) · 2023Article
- Metabolic modeling of sex-specific tissue predicts mechanisms of differences in toxicological responses.bioRxiv : the preprint server for biology · 2023Article
- Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2.Stem cell research & therapy · 2022Article
- The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2.Experimental & molecular medicine · 2021Article
- Mechanistic models of microbial community metabolism.Molecular omics · 2021Review
- Predicting changes in renal metabolism after compound exposure with a genome-scale metabolic model.Toxicology and applied pharmacology · 2021Article
- Toxicant-Induced Metabolic Alterations in Lipid and Amino Acid Pathways Are Predictive of Acute Liver Toxicity in Rats.International journal of molecular sciences · 2020Article
- Genome-Scale Characterization of Toxicity-Induced Metabolic Alterations in Primary Hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Context-specific GEnome-scale metabolic Network REconstructions (GENREs) provide a means to understand cellular metabolism at a deeper level of physiological detail. Here, we use transcriptomics data from chemically-exposed rat hepatocytes to constrain a GENRE of rat hepatocyte metabolism and predict biomarkers of liver toxicity using the Transcriptionally Inferred Metabolic Biomarker Response algorithm. We profiled alterations in cellular hepatocyte metabolism following in vitro exposure to four toxicants (acetaminophen, carbon tetrachloride, 2,3,7,8-tetrachlorodibenzodioxin, and trichloroethylene) for six hour. TIMBR predictions were compared with paired fresh and spent media metabolomics data from the same exposure conditions. Agreement between computational model predictions and experimental data led to the identification of specific metabolites and thus metabolic pathways associated with toxicant exposure. Here, we identified changes in the TCA metabolites citrate and alpha-ketoglutarate along with changes in carbohydrate metabolism and interruptions in ATP production and the TCA Cycle. Where predictions and experimental data disagreed, we identified testable hypotheses to reconcile differences between the model predictions and experimental data. The presented pipeline for using paired transcriptomics and metabolomics data provides a framework for interrogating multiple omics datasets to generate mechanistic insight of metabolic changes associated with toxicological responses.
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