Proposal for a chemically consistent way to annotate ions arising from the analysis of reference compounds under ESI conditions: A prerequisite to proper mass spectral database constitution in metabolomics

Abstract

Nowadays, high‐resolution mass spectrometry is widely used for metabolomic studies. Thanks to its high sensitivity, it enables the detection of a large range of metabolites. In metabolomics, the continuous quest for a metabolite identification as complete and accurate as possible has led during the last decade to an ever increasing development of public MS databases (including LC‐MS data) concomitantly with bioinformatic tool expansion. To facilitate the annotation process of MS profiles obtained from biological samples, but also to ease data sharing, exchange, and exploitation, the standardization and harmonization of the way to describe and annotate mass spectra seemed crucial to us. Indeed, under electrospray (ESI) conditions, a single metabolite does not produce a unique ion corresponding to its protonated or deprotonated form but could lead to a complex mixture of signals. These MS signals result from the existence of different natural isotopologues of the same compound and also to the potential formation of adduct ions, homomultimeric and heteromultimeric ions, fragment ions resulting from “prompt” in‐source dissociations. As a joint reflection process within the French Infrastructure for Metabolomics and Fluxomics (MetaboHUB) and with the purpose of developing a robust and exchangeable annotated MS database made from pure reference compounds (chemical standards) analysis, it appeared to us that giving the metabolomics community some clues to standardize and unambiguously annotate each MS feature was a prerequisite to data entry and further efficient querying of the mass spectral database. The use of a harmonized notation is also mandatory for interlaboratory MS data exchange. Additionally, thorough description of the variety of MS signals arising from the analysis of a unique metabolite might provide greater confidence on its annotation.

Combining Chemical Knowledge and Quantum Calculation for Interpreting Low-Energy Product Ion Spectra of Metabolite Adduct Ions: Sodiated Diterpene Diester Species as a Case Study

“…It is necessary to consider chemically-compatible annotations of the desorbed sodiated molecules at the origin of CBCs. 16 Indeed, two possible structures can be considered: (i) charge solvated forms (i.e., Na + liganded by heteroatom(s) annotated as [M+Na] + ) and (ii) protonated salts annotated as zwitterionic species [(M-H+Na)+H] + with the mobile proton located at the heteroatoms. 16 When submitted to CID, the former species would yield exclusively free Na + , 10,[12][13][14] while the protonated salt would dissociate directly or indirectly (by prototropy) by CBC(s) with salt retention either on product ions or attached to lost neutrals.…”

“…16 Indeed, two possible structures can be considered: (i) charge solvated forms (i.e., Na + liganded by heteroatom(s) annotated as [M+Na] + ) and (ii) protonated salts annotated as zwitterionic species [(M-H+Na)+H] + with the mobile proton located at the heteroatoms. 16 When submitted to CID, the former species would yield exclusively free Na + , 10,[12][13][14] while the protonated salt would dissociate directly or indirectly (by prototropy) by CBC(s) with salt retention either on product ions or attached to lost neutrals. 15 Thus, the objective of the present letter is to propose alternative mechanisms to the CRF/CMF ones based solely on interpreting the chemistry of Na + retention either in product ions or neutral losses occurring during fragmentation of sodiated molecules.…”

A European proposal for quality control and quality assurance of tandem mass spectral libraries

“…Curation efforts may include noise and artifact removal, recalibration of spectra and peak annotations, manual inspection of mass spectra by experienced mass spectrometrists, as well as inter-library comparisons (e.g., [15,25,27,61]). Removal of noise during data processing may lead to losses of spectral information of compounds.…”

Electrospray ionization and heterogeneous matrix effects in liquid chromatography/mass spectrometry based meta‐metabolomics: A biomarker or a suppressed ion?

“…Those studies were in the 100.00 † Feature code represents the ion's nominal m/z value preceded by "M," and ion's retention time (in seconds) preceded by "T". ‡ Adducts are annotated following the proposal of Damont et al 19 a, b, c: Features belonging to a same metabolite (based on "CAMERA" annotations). N/A: not available.…”

“…In this context, the present work focuses on a widely known type of matrix effect: the "ion suppression" phenomenon. This is an analytical/instrumental drift mainly observed during LC/MS-based metabolomics experiments, in particular when the applied ionization mode is the commonly used 19 Electrospray Ionization (ESI) source (also for Atmospheric Pressure Chemical Ionization)…”