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Nontargeted identification of tracer incorporation in high-resolution mass spectrometry

Authors

  • F. Hoffmann
  • C. Jaeger
  • A. Bhattacharya
  • C.A. Schmitt
  • J. Lisec

Journal

  • Analytical Chemistry

Citation

  • Anal Chem 90 (12): 7253-7260

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 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, non-redundant list of all compounds showing more than 1% tracer incorporation in a non-targeted 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 non-informative 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 LC-ESI to demonstrate broad applicability of our tool and emphasize importance of QC tests. HiResTEC is provided as a package in the open source software framework R and is freely available on CRAN.


DOI

doi:10.1021/acs.analchem.8b00356