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Compound annotation in liquid chromatography/high-resolution mass spectrometry based metabolomics: robust adduct ion determination as a prerequisite to structure prediction in electrospray ionization mass spectra

Item Type:Article
Title:Compound annotation in liquid chromatography/high-resolution mass spectrometry based metabolomics: robust adduct ion determination as a prerequisite to structure prediction in electrospray ionization mass spectra
Creators Name:Jaeger, C. and Méret, M. and Schmitt, C.A. and Lisec, J.
Abstract:RATIONALE: A bottleneck in metabolic profiling of complex biological extracts is confident, non-supervised annotation of ideally all contained, chemically highly diverse small molecules. Recent computational strategies combining sum formula prediction with in silico fragmentation achieve confident de novo annotation, once the correct neutral mass of a compound is known. Current software solutions for automated adduct ion assignment, however, are either publicly unavailable or have been validated against only few experimental electrospray ionization (ESI) mass spectra. METHODS: We here present findMAIN (find Main Adduct IoN) a new heuristic approach for interpreting ESI mass spectra. findMAIN scores MS(1) spectra based on explained intensity, mass accuracy and isotope charge agreement of adducts and related ionization products and annotates peaks of the (de)protonated molecule and adduct ions. The approach was validated against 1,141 ESI positive mode spectra of chemically diverse standard compounds acquired on different high-resolution mass spectrometric instruments (Orbitrap and time-of-flight). Robustness against impure spectra was evaluated. RESULTS: Correct adduct ion assignment was achieved for up to 83% of the spectra. Performance was independent of compound class and mass spectrometric platform. The algorithm proved highly tolerant against spectral contamination as demonstrated exemplarily for co-eluting compounds as well as systematically by pairwise mixing of spectra. When used in conjunction with MS-FINDER, a state-of-the-art sum formula tool, correct sum formulas were obtained for 77% of spectra. It outperformed both 'brute force' approaches and current state-of-the-art annotation packages tested as potential alternatives. Limitations of the heuristic pertained to poorly ionizing compounds and cationic compounds forming [M](+) ions. CONCLUSIONS: A new, validated approach for interpreting ESI mass spectra is presented, filling a gap in the nontargeted metabolomics workflow. It is freely available in the latest version of R package InterpretMSSpectrum (https://cran.r-project.org).
Keywords:Metabolomics, Nontarget Workflow, Annotation, Electrospray Ionization, High-Resolution Mass Spectrometry
Source:Rapid Communications in Mass Spectrometry
ISSN:0951-4198
Publisher:Wiley-Blackwell (U.K.)
Volume:31
Number:15
Page Range:1261-1266
Date:15 August 2017
Official Publication:https://doi.org/10.1002/rcm.7905
PubMed:View item in PubMed

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