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Author Notes:

Corresponding Author: Department of Medicine, Pulmonary Division, Emory University, 205 Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322. Tel: 404-727-5970. Fax: 404-712-2974. dpjones@emory.edu.

The authors declare no competing financial interest.

Subject:

Research Funding:

The authors acknowledge support by NIH grants ES023485, ES019776, HL113451, OD018006, AG038746, ES025632, and HL086773, California Breast Cancer Research Program 21UB-8002, and NIH contracts 1U2CES026560-01, HHSN272201200031C, and HHSN27200009.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physical Sciences
  • Chemistry, Medicinal
  • Chemistry, Multidisciplinary
  • Toxicology
  • Pharmacology & Pharmacy
  • Chemistry
  • MOBILITY-MASS-SPECTROMETRY
  • HIGH-RESOLUTION METABOLOMICS
  • PERFORMANCE LIQUID-CHROMATOGRAPHY
  • IN-SILICO FRAGMENTATION
  • WIDE ASSOCIATION
  • MILITARY PERSONNEL
  • LARGE-SCALE
  • STRUCTURAL-CHARACTERIZATION
  • PROBABILISTIC ANNOTATION
  • CHIRAL SEPARATIONS

Computational Metabolomics: A Framework for the Million Metabolome

Tools:

Journal Title:

Chemical Research in Toxicology

Volume:

Volume 29, Number 12

Publisher:

, Pages 1956-1975

Type of Work:

Article | Post-print: After Peer Review

Abstract:

"Sola dosis facit venenum." These words of Paracelsus, "the dose makes the poison", can lead to a cavalier attitude concerning potential toxicities of the vast array of low abundance environmental chemicals to which humans are exposed. Exposome research teaches that 80-85% of human disease is linked to environmental exposures. The human exposome is estimated to include >400,000 environmental chemicals, most of which are uncharacterized with regard to human health. In fact, mass spectrometry measures >200,000 m/z features (ions) in microliter volumes derived from human samples; most are unidentified. This crystallizes a grand challenge for chemical research in toxicology: to develop reliable and affordable analytical methods to understand health impacts of the extensive human chemical experience. To this end, there appears to be no choice but to abandon the limitations of measuring one chemical at a time. The present review looks at progress in computational metabolomics to provide probability-based annotation linking ions to known chemicals and serve as a foundation for unambiguous designation of unidentified ions for toxicologic study. We review methods to characterize ions in terms of accurate mass m/z, chromatographic retention time, correlation of adduct, isotopic and fragment forms, association with metabolic pathways and measurement of collision-induced dissociation products, collision cross section, and chirality. Such information can support a largely unambiguous system for documenting unidentified ions in environmental surveillance and human biomonitoring. Assembly of this data would provide a resource to characterize and understand health risks of the array of low-abundance chemicals to which humans are exposed.

Copyright information:

© 2016 American Chemical Society.

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