Challenges in Identifying the Dark Molecules of Life

Annu Rev Anal Chem (Palo Alto Calif). 2019 Jun 12;12(1):177-199. doi: 10.1146/annurev-anchem-061318-114959. Epub 2019 Mar 18.


Metabolomics is the study of the metabolome, the collection of small molecules in living organisms, cells, tissues, and biofluids. Technological advances in mass spectrometry, liquid- and gas-phase separations, nuclear magnetic resonance spectroscopy, and big data analytics have now made it possible to study metabolism at an omics or systems level. The significance of this burgeoning scientific field cannot be overstated: It impacts disciplines ranging from biomedicine to plant science. Despite these advances, the central bottleneck in metabolomics remains the identification of key metabolites that play a class-discriminant role. Because metabolites do not follow a molecular alphabet as proteins and nucleic acids do, their identification is much more time consuming, with a high failure rate. In this review, we critically discuss the state-of-the-art in metabolite identification with specific applications in metabolomics and how technologies such as mass spectrometry, ion mobility, chromatography, and nuclear magnetic resonance currently contribute to this challenging task.

Keywords: chromatography; ion mobility; metabolite identification; metabolomics; nuclear magnetic resonance spectroscopy; tandem mass spectrometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Chromatography, Liquid / methods
  • Humans
  • Ion Mobility Spectrometry / methods
  • Magnetic Resonance Spectroscopy / methods
  • Mass Spectrometry / methods
  • Metabolome*
  • Metabolomics / methods*