Metabolomics as a Truly Translational Tool for Precision Medicine

• Type of Material: Article
• Authors: Julian C Schmidt, Sovaris Aerospace; Bonnie V Dougherty, University of Virginia; Richard D Beger, US Food and Drug Administration; Dean Jones, Emory University; Michael A Schmidt, Sovaris Aerospace; William B Mattes, US Food and Drug Administration
• Language: English
• Date: 2021-10-01
• Publisher: SAGE PUBLICATIONS INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author(s) 2021.
• Final Published Version (URL): http://dx.doi.org/10.1177/10915818211039436
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF TOXICOLOGY
• Volume: 40
• Issue: 5
• Start Page: 413
• End Page: 426
• Grant/Funding Information: DPJ was supported in part by NIH grants ES023485, ES031824, ES019776, ES030163, ES029490, ES032189 and DoD grant W81XWH2010103. The opinions expressed in this manuscript do not necessarily represent those of the US the Food and Drug Administration.; The NASA Twins Study of one year in space was supported by NASA: NNX14AH51G (All Twins PIs); TRISH: NNX16AO69A:0107 and NNX16AO69A:0061; the Bert L and N Kuggie Vallee Foundation, the WorldQuant Foundation, The Pershing Square Sohn Cancer Research Alliance, and the Bill and Melinda Gates Foundation (OPP1151054) for funding.
• Keywords: SERUM BILE-ACID; Pharmacology & Pharmacy; METABOLISM; LIVER-INJURY; metabolomics; ACETAMINOPHEN TOXICITY; PROFILES; BIOMARKERS; precision medicine; toxicity; Science & Technology; Life Sciences & Biomedicine; Toxicology; IDENTIFICATION

Abstract

Metabolomics is unique among omics technologies in being applicable to metabolism and toxicity studies broadly across organisms (e.g., humans, other mammals, model organisms, and even bacteria) and across biological materials (e.g., blood, urine, saliva, biopsy, and stool), including cultured cells and subcellular fractions. Metabolomics can be used to characterize biologic response patterns in humans as well as to support mechanistic studies in model systems and ex vivo studies. A broad range of resources are available, including publicly accessible data repositories (e.g., Metabolomics Workbench), tools for biostatistics and bioinformatics (e.g., MetaboAnalyst), metabolite identification (e.g., Metlin), and pathway analysis (e.g., Kyoto Encyclopedia of Genes and Genomes). Thus, metabolomics is more than a promise of the future; metabolomics is already available as a translational approach to facilitate precision medicine. This ACT Symposium review will contain an introduction to metabolomics in toxicity studies followed by sections on translational metabolic networks, translational metabolite biomarkers of acetaminophen-induced acute liver injury, translational framework using high-resolution metabolomics for integrated pharmacokinetics and pharmacodynamics, and precision medicine applications: extracting actionable targets from untargeted metabolomics data following one year in space.