Annotation of Metabolites in Stable Isotope Tracing Untargeted Metabolomics via Khipu-web.
Document Type
Article
Publication Date
12-4-2024
Original Citation
Mitchell J,
Chi Y,
Zheng S,
Thapa M,
Wang E,
Li S.
Annotation of Metabolites in Stable Isotope Tracing Untargeted Metabolomics via Khipu-web. J Am Soc Mass Spectrom. 2024;35(12):2824-35.
Keywords
JGM, Metabolomics, Isotope Labeling, Software, Internet, Mass Spectrometry, Metabolome, Humans
JAX Source
J Am Soc Mass Spectrom. 2024;35(12):2824-35.
ISSN
1879-1123
PMID
39348378
DOI
https://doi.org/10.1021/jasms.4c00175
Grant
This work was in part funded by NIH grants (to S.L.) U01 CA235493 (NCI) and R01 AI149746 (NIAID)
Abstract
Stable isotope tracing is a crucial technique for understanding the metabolic wiring of biological systems, determining metabolic flux through pathways of interest, and detecting novel metabolites and pathways. Despite the potential insights provided by this technique, its application remains limited to a small number of targeted molecules and pathways. Because previous software tools usually require chemical formulas to find relevant features, and the data are highly complex, especially in untargeted metabolomics and when the downstream reactions and metabolites are poorly characterized. We report here Khipu version 2 and its new user-friendly web application. New functions are added to enhance analyzing stable isotope tracing data including metrics that evaluate peak enrichment in labeled samples, scoring methods to facilitate robust detection of intensity patterns and integrated natural abundance correction. We demonstrate that this approach can be applied to untargeted metabolomics to systematically extract isotope-labeled compounds and annotate the unidentified metabolites.