SIMPEL tool to elucidate dynamics of complex metabolism

Cellular metabolism involves flux through metabolic routes, which can be measured using stable isotope (¹³C,¹⁵N) tracers. High-resolution mass spectrometry (HRMS) and transient isotope labeling studies offer an opportunity to get an in-depth understanding of metabolism in specific contexts. In this new work, Kambhampati et al. introduce Stable Isotope-assisted Metabolomics for Pathway Elucidation (SIMPEL) as a new tool that advances the analysis and interpretation of isotope-enriched HRMS datasets to elucidate operational metabolic pathways. SIMPEL is a data analysis tool that uses accurate mass information to group and compare isotope labeling and to cluster enriched metabolites based on their precursor-product relationships. It enables the detection and quantification of isotopically labeled metabolites in untargeted HRMS datasets for the exploration and characterization of new metabolic processes. The authors demonstrate SIMPEL’s effectiveness by two studies, a dual-isotope labeling flux experiment and a single-label lipidomic analysis. The SIMPEL tool is available in the R package and expands metabolomics investigations by including isotopologue signatures that are essential for quantifying metabolic flux. (Summary by Maneesh Lingwan @LingwanManeesh) Commun. Biol. 10.1038/s42003-024-05844-z