Abstract
The annotation of small molecules remains a major challenge in untargeted mass spectrometry-based metabolomics. We here critically discuss structured elucidation approaches and software that are designed to help during the annotation of unknown compounds. Only by elucidating unknown metabolites first is it possible to biologically interpret complex systems, to map compounds to pathways and to create reliable predictive metabolic models for translational and clinical research. These strategies include the construction and quality of tandem mass spectral databases such as the coalition of MassBank repositories and investigations of MS/MS matching confidence. We present in silico fragmentation tools such as MS-FINDER, CFM-ID, MetFrag, ChemDistiller and CSI:FingerID that can annotate compounds from existing structure databases and that have been used in the CASMI (critical assessment of small molecule identification) contests. Furthermore, the use of retention time models from liquid chromatography and the utility of collision cross-section modelling from ion mobility experiments are covered. Workflows and published examples of successfully annotated unknown compounds are included.
Highlights
Metabolomics is the comprehensive study of small molecules present in cells, tissues and body fluids
High resolution chromatographic separation techniques coupled to accurate tandem mass spectrometry (LC-MS/MS) represents the most important metabolomics platform
The drug Indomethacin for the proton adduct has a reported cross-section values (CCS) value of 183.54 Å2 measured on a drift tube IMS (DTIMS) [139]; the same compound has a CCS value of 179.039 Å2 measured on a traveling wave ion mobility spectrometry (TWIMS) setup, and the predicted value is 197.7 Å2 and falls outside the 3% median prediction error [164]
Summary
Metabolomics is the comprehensive study of small molecules present in cells, tissues and body fluids. More common are ‘Level 1’ annotations that are confirmed by two orthogonal parameters, Classical structure elucidation using NMR commonly elucidates the full structure using de‐novo such as retention time and MS/MS spectrum These levels were initially forged by the Metabolomics approaches [10]. Common are ‘Level 1’ annotations that are confirmed by two orthogonal parameters, such as retention time and MS/MS spectrum These levels were initially forged by the Metabolomics (MSI) ofas the [14,15]Identification and were confidence levelsStandards of compound annotations, discussed by theSociety. A number of reviews have been published that cover many diverse metabolomics topics discuss structure elucidation approaches involving liquid chromatography tandem mass spectrometry including chromatography, data processing and statistics in great detail [16,17,18,19,20,21,22,23,24].
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