A mass spectrum-oriented computational method for ion mobility-resolved untargeted metabolomics
Open Access
- 31 March 2023
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 14 (1), 1-15
- https://doi.org/10.1038/s41467-023-37539-0
Abstract
Ion mobility (IM) adds a new dimension to liquid chromatography-mass spectrometry-based untargeted metabolomics which significantly enhances coverage, sensitivity, and resolving power for analyzing the metabolome, particularly metabolite isomers. However, the high dimensionality of IM-resolved metabolomics data presents a great challenge to data processing, restricting its widespread applications. Here, we develop a mass spectrum-oriented bottom-up assembly algorithm for IM-resolved metabolomics that utilizes mass spectra to assemble four-dimensional peaks in a reverse order of multidimensional separation. We further develop the end-to-end computational framework Met4DX for peak detection, quantification and identification of metabolites in IM-resolved metabolomics. Benchmarking and validation of Met4DX demonstrates superior performance compared to existing tools with regard to coverage, sensitivity, peak fidelity and quantification precision. Importantly, Met4DX successfully detects and differentiates co-eluted metabolite isomers with small differences in the chromatographic and IM dimensions. Together, Met4DX advances metabolite discovery in biological organisms by deciphering the complex 4D metabolomics data.This publication has 52 references indexed in Scilit:
- Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular NetworkingNature Biotechnology, 2016
- Hydrogen Rearrangement Rules: Computational MS/MS Fragmentation and Structure Elucidation Using MS-FINDER SoftwareAnalytical Chemistry, 2016
- Ion Mobility-Mass Spectrometry: Time-Dispersive InstrumentationAnalytical Chemistry, 2014
- Metabolite identification: are you sure? And how do your peers gauge your confidence?Metabolomics, 2014
- Ion Mobility Derived Collision Cross Sections to Support Metabolomics ApplicationsAnalytical Chemistry, 2014
- Ion dynamics in a trapped ion mobility spectrometerThe Analyst, 2014
- Metabolomics: the apogee of the omics trilogyNature Reviews Molecular Cell Biology, 2012
- MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile dataBMC Bioinformatics, 2010
- Proposed minimum reporting standards for chemical analysisMetabolomics, 2007
- XCMS: Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and IdentificationAnalytical Chemistry, 2006