Reactomics: Using mass spectrometry as a chemical reaction detector

Abstract

Chemical reactions among small molecules enable untargeted metabolomics analysis, in which small molecules within tissue samples are identified through high-throughput assays. In standard mass spectrometry-based metabolomics, first significant small molecules are identified, then their biochemical relationships are probed to reveal biological fate (environmental studies) or biological impact (physiological response). However, we propose that biochemical relationships could be directly retrieved through untargeted high-resolution paired mass distance (PMD), which investigates chemical pairs in the samples without a priori knowledge of the identities of those participating compounds. We present the potential for this chemical reaction detector, or ‘reactomics’ approach, linking PMD from the mass spectrometer to biochemical reactions obtained via data mining of known small molecular metabolites/compounds and reaction databases. This approach encompasses both quantitative and qualitative analysis of reaction by mass spectrometry, and its potential applications include PMD network analysis, source appointment of unknown compounds, and biomarker reaction discovery instead of compound discovery. Such applications may promote novel biological discoveries that are not currently possible with classical chemical analysis.