RT Journal Article
SR Electronic
T1 Reactomics: Using mass spectrometry as a chemical reaction detector
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 855148
DO 10.1101/855148
A1 Miao Yu
A1 Lauren Petrick
YR 2019
UL http://biorxiv.org/content/early/2019/12/24/855148.abstract
AB 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.Significance Statement Chemical reactions can describe the relationships among molecules. If we could directly measure chemical reactions, the identification of unknown molecules in the living system could be bypassed in metabolomics studies. In this work we propose “reactomics”, a concept that uses a paired mass distances (PMD) profile among mass spectrometry measured peaks to perform quantitatively and qualitatively analysis of reactions in the samples. For example, peaks involved in a PMD 15.995 Da imply an oxidation process, and changes in levels of these reactions can be used to investigate living processes. We developed the pmd package to perform reactomics analysis including screening unknown metabolites linked with exposure, source appointment of unknown peaks, and biomarker reaction discovery for lung cancer.