Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases

Liang Cui, Haitao Lu, Yie Hou Lee*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

198 Citations (Scopus)


In the past decade, advances in liquid chromatography-mass spectrometry (LC-MS) have revolutionized untargeted metabolomics analyses. By mining metabolomes more deeply, researchers are now primed to uncover key metabolites and their associations with diseases. The employment of untargeted metabolomics has led to new biomarker discoveries and a better mechanistic understanding of diseases with applications in precision medicine. However, many major pertinent challenges remain. First, compound identification has been poor, and left an overwhelming number of unidentified peaks. Second, partial, incomplete metabolomes persist due to factors such as limitations in mass spectrometry data acquisition speeds, wide-range of metabolites concentrations, and cellular/tissue/temporal-specific expression changes that confound our understanding of metabolite perturbations. Third, to contextualize metabolites in pathways and biology is difficult because many metabolites partake in multiple pathways, have yet to be described species specificity, or possess unannotated or more-complex functions that are not easily characterized through metabolomics analyses. From a translational perspective, information related to novel metabolite biomarkers, metabolic pathways, and drug targets might be sparser than they should be. Thankfully, significant progress has been made and novel solutions are emerging, achieved through sustained academic and industrial community efforts in terms of hardware, computational, and experimental approaches. Given the rapidly growing utility of metabolomics, this review will offer new perspectives, increase awareness of the major challenges in LC-MS metabolomics that will significantly benefit the metabolomics community and also the broader the biomedical community metabolomics aspire to serve.

Original languageEnglish
Pages (from-to)772-792
Number of pages21
JournalMass Spectrometry Reviews
Issue number6
Early online date27 Feb 2018
Publication statusPublished - Nov 2018

Scopus Subject Areas

  • Analytical Chemistry
  • Condensed Matter Physics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Spectroscopy

User-Defined Keywords

  • disease
  • liquid chromatography
  • mass spectrometry
  • medicine
  • metabolomics
  • untargeted metabolomics


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