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- Maximilian J. Helf
- Bennett W. Fox
- Alexander B. Artyukhin
- Ying K. Zhang
- Frank C. Schroeder
Untargeted metabolomics via mass spectrometry (MS) can reveal several 100,000 molecular features in a single sample, most of which may represent unidentified metabolites, posing significant challenges to data analysis. We here introduce Metaboseek, an open-source analysis platform designed for untargeted comparative metabolomics, and demonstrate its utility to elucidate functions of a conserved fat metabolism pathway, α-oxidation, using C. elegans as a model. Metaboseek integrates modules for molecular feature detection, statistics, molecular formula prediction, and MS/MS analysis, which uncovered more than >200 previously uncharacterized α-oxidation-dependent metabolites in an untargeted comparison of wildtype and α-oxidation-defective hacl-1 mutants. The identified structures support the predicted enzymatic function of HACL-1 and revealed that α-oxidation participates in metabolism of endogenous β-methyl-branched fatty acids and food-derived cyclopropane lipids. Our results showcase compound discovery via untargeted comparative metabolomics applied to a conserved primary metabolic pathway and suggest a model for the metabolism of cyclopropane lipids that are also part of human diets.