Metabomatching: Using genetic association to identify metabolites in proton NMR spectroscopy.
Détails
Télécharger: BIB_C001C1DFA970.pdf (2546.03 [Ko])
Etat: Public
Version: Final published version
Etat: Public
Version: Final published version
ID Serval
serval:BIB_C001C1DFA970
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Metabomatching: Using genetic association to identify metabolites in proton NMR spectroscopy.
Périodique
PLoS computational biology
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Statut éditorial
Publié
Date de publication
12/2017
Peer-reviewed
Oui
Volume
13
Numéro
12
Pages
e1005839
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
A metabolome-wide genome-wide association study (mGWAS) aims to discover the effects of genetic variants on metabolome phenotypes. Most mGWASes use as phenotypes concentrations of limited sets of metabolites that can be identified and quantified from spectral information. In contrast, in an untargeted mGWAS both identification and quantification are forgone and, instead, all measured metabolome features are tested for association with genetic variants. While the untargeted approach does not discard data that may have eluded identification, the interpretation of associated features remains a challenge. To address this issue, we developed metabomatching to identify the metabolites underlying significant associations observed in untargeted mGWASes on proton NMR metabolome data. Metabomatching capitalizes on genetic spiking, the concept that because metabolome features associated with a genetic variant tend to correspond to the peaks of the NMR spectrum of the underlying metabolite, genetic association can allow for identification. Applied to the untargeted mGWASes in the SHIP and CoLaus cohorts and using 180 reference NMR spectra of the urine metabolome database, metabomatching successfully identified the underlying metabolite in 14 of 19, and 8 of 9 associations, respectively. The accuracy and efficiency of our method make it a strong contender for facilitating or complementing metabolomics analyses in large cohorts, where the availability of genetic, or other data, enables our approach, but targeted quantification is limited.
Mots-clé
Databases, Genetic, Genome-Wide Association Study/methods, Humans, Magnetic Resonance Spectroscopy/methods, Metabolomics/methods
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/12/2017 15:57
Dernière modification de la notice
20/08/2019 15:34