title: Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.
abstract: The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Martin
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Maillot
authors.affiliation: INRA, UMR 1083 SPO, INRA Campus SupAgro, Plateforme Polyphénols, 2 Place Viala, 34060 Montpellier Cedex 02, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Mazerolles
authors.affiliation: BRUKER, 4 allée Hendrick Lorentz, 77447 Marne La Vallée Cedex 2, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Verdu
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lyan
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Migné
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.affiliation: INRA, UMR 1331 TOXALIM (Research Center in Food Toxicology), Axiom-Metatoul, 31027 Toulouse, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Canlet
authors.affiliation: Laboratoire d'Etude du Métabolisme des Médicaments, DSV/iBiTec-S/SPI, CEA-Saclay, 91191 Gif-sur-Yvette Cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Junot
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Via Enrico Fermi 2749, 21027 Ispra, Italy.
authors.forename: Claude
authors.initials: C
authors.lastname: Guillou
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Manach
authors.affiliation: INRA, UMR1332 Fruit Biology and Pathology, Centre INRA de Bordeaux, 33140 Villenave d'Ornon, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jabob
authors.affiliation: INRA, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France ; AgroParisTech, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France.
authors.forename: Delphine Jouan-Rimbaud
authors.initials: DJ
authors.lastname: Bouveresse
authors.affiliation: INRA, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France ; AgroParisTech, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Paris
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Pujos-Guillot
authors.affiliation: INRA, UMR 1331 TOXALIM (Research Center in Food Toxicology), Metabolism of Xenobiotics (MeX), 31027 Toulouse, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Jourdan
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Giacomoni
authors.affiliation: LUNAM Université, Oniris, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, BP 50707, 44307 Nantes Cedex 3, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Courant
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Favé
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA UK.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Le Gall
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Via Enrico Fermi 2749, 21027 Ispra, Italy.
authors.forename: Hubert
authors.initials: H
authors.lastname: Chassaigne
authors.affiliation: UPMC, Institut Parisien de Chimie Moléculaire, UMR-CNRS 7201, 4 Place Jussieu, Paris Cédex 05, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tabet
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, 63000 Clermond-Ferrand, France ; INRA, UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, 63000 Clermond-Ferrand, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Martin
authors.affiliation: LUNAM Université, Oniris, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, BP 50707, 44307 Nantes Cedex 3, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Antignac
authors.affiliation: Aix-Marseille Université, ISM2, Campus Scientifique Saint Jérôme, 13397 Marseille Cedex 20, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Shintu
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Defernez
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Philo
authors.affiliation: Aix-Marseille Université, ISM2, Campus Scientifique Saint Jérôme, 13397 Marseille Cedex 20, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Alexandre-Gouaubau
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Marie-Josephe
authors.initials: MJ
authors.lastname: Amiot-Carlin
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Via Enrico Fermi 2749, 21027 Ispra, Italy.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Bossis
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), 93017 Bobigny, France.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Triba
authors.affiliation: LCH, Laboratoire des Courses Hippiques, 91370 Verrières-le-Buisson, France.
authors.forename: Natali
authors.initials: N
authors.lastname: Stojilkovic
authors.affiliation: AP-HM, Hôpital Timone, Laboratoire de Biochimie, 13385 Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Banzet
authors.affiliation: Université de Picardie Jules Verne, EA 3900 BIOPI Biologie des plantes innovation, UFR de Pharmacie, 1 rue des Louvels, 80000 Amiens, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Molinié
authors.affiliation: INRA UMR1260, "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France ; Faculté de Médecine, Aix-Marseille Université, 13385 Marseille, France ; INSERM, UMR1062 "Nutrition, Obésité et Risque Thrombotique", 13385 Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
authors.affiliation: MetaboMer, FR2424, CNRS/UPMC, Station Biologique de Roscoff, Place Georges Tessier, 29680 Roscoff, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Goulitquer
authors.affiliation: Aix-Marseille Université, ISM2, Campus Scientifique Saint Jérôme, 13397 Marseille Cedex 20, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caldarelli
authors.affiliation: INRA, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France ; AgroParisTech, UMR 1145 Ingénierie Procédés Aliments, 75005 Paris, France.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Rutledge
keywords: Inter-laboratory; Mass spectrometry; Metabolic fingerprinting; Nuclear magnetic resonance; Untargeted metabolomics