Nontargeted Identification of Tracer Incorporation in High-Resolution Mass Spectrometry
- Friederike HoffmannFriederike HoffmannCharité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology, and Tumor Immunology and Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, GermanyMore by Friederike Hoffmann,
- Carsten JaegerCarsten JaegerCharité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology, and Tumor Immunology and Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, GermanyBerlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, GermanyMore by Carsten Jaeger,
- Animesh BhattacharyaAnimesh BhattacharyaCharité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology, and Tumor Immunology and Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, GermanyMore by Animesh Bhattacharya,
- Clemens A. SchmittClemens A. SchmittCharité-Universitätsmedizin Berlin, Medical Department of Hematology, Oncology, and Tumor Immunology and Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, GermanyBerlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, GermanyMax-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125 Berlin, GermanyMore by Clemens A. Schmitt, and
- Jan Lisec*Jan Lisec*E-mail: [email protected]. Fax: +49 (30) 8104-75891.Federal Institute for Materials Research and Testing (BAM), Division 1.7 Analytical Chemistry, Richard-Willstätter-Straße 11, 12489 Berlin, GermanyMore by Jan Lisec
Abstract

“Fluxomics” refers to the systematic analysis of metabolic fluxes in a biological system and may uncover novel dynamic properties of metabolism that remain undetected in conventional metabolomic approaches. In labeling experiments, tracer molecules are used to track changes in the isotopologue distribution of metabolites, which allows one to estimate fluxes in the metabolic network. Because unidentified compounds cannot be mapped on pathways, they are often neglected in labeling experiments. However, using recent developments in de novo annotation may allow to harvest the information present in these compounds if they can be identified. Here, we present a novel tool (HiResTEC) to detect tracer incorporation in high-resolution mass spectrometry data sets. The software automatically extracts a comprehensive, nonredundant list of all compounds showing more than 1% tracer incorporation in a nontargeted fashion. We explain and show in an example data set how mass precision and other filter heuristics, calculated on the raw data, can efficiently be used to reduce redundancy and noninformative signals by 95%. Ultimately, this allows to quickly investigate any labeling experiment for a complete set of labeled compounds (here 149) with acceptable false positive rates. We further re-evaluate a published data set from liquid chromatography-electrospray ionization (LC-ESI) to demonstrate broad applicability of our tool and emphasize importance of quality control (QC) tests. HiResTEC is provided as a package in the open source software framework R and is freely available on CRAN.
Cited By
This article is cited by 2 publications.
- Manohar C. Dange, Vivek Mishra, Bratati Mukherjee, Damini Jaiswal, Murtaza S. Merchant, Charulata B. Prasannan, Pramod P. Wangikar. Evaluation of freely available software tools for untargeted quantification of 13C isotopic enrichment in cellular metabolome from HR-LC/MS data. Metabolic Engineering Communications 2020, 10 , e00120. https://doi.org/10.1016/j.mec.2019.e00120
- Elizabeth M. Llufrio, Kevin Cho, Gary J. Patti. Systems-level analysis of isotopic labeling in untargeted metabolomic data by X13CMS. Nature Protocols 2019, 14 (7) , 1970-1990. https://doi.org/10.1038/s41596-019-0167-1




