Recent Technical Advancement in High-Resolution Metabolomics

Metabolomics refers to the study of small molecules in biologic systems. Earlier technologies were restricted in sensitivity and only detected hundreds of chemicals, but contemporary ultra-high-resolution mass spectrometry coupled to liquid chromatography, gas chromatography and other separation techniques, show that the metabolome of humans and other species consists of hundreds of thousands of chemicals derived from endogenous metabolism, food, microbial symbionts and infectious agents, and chemicals from environmental exposures. Coupling exposure science measures of exogenous chemicals with high-resolution metabolomics (HRM) for biomonitoring of environmental chemicals and metabolites has considerably facilitated interpretation of low abundance signals, which are often present at three to five orders of magnitude lower abundance than endogenous metabolites. Current HRM methods rely upon multiple technical replicates with advanced instrumentation for separation, ionization and detection, along with data extraction and computational methods. Fourier-transform instruments (e.g., orbitrap MS, Ion-Cyclotron Resonance MS) enable measurement of tens of thousands of chemicals with accurate mass m/z within 5 ppm mass resolution and mass accuracy. Computational methods and big data tools are being used to curate this extensive number of low abundance signals and connect these chemical signals to metabolic responses, biomarkers of risk and impacts on disease phenotype.