Can we Trust Untargeted Metabolomics: Results of the Metabo-ring Initiative, a Large-scale Multi-instruments Inter-laboratoire Study

Jean-Charles Martin (1) , Mathieu Maillot (1) , Gerard Mazerolles (2) , Alexandre Verdu (3) , Bernard Lyan (4) , Carole Migné (4) , Catherine Defoort (1) , Cécile Canlet (5) , Christophe Junot (6) , Claude Guillou (7) , Claudine Manach (4) , Daniel Jabob (8) , Delphine Jouan-Rimbaud Bouveresse (9) , Estelle Rathahao-Paris (9) , Estelle Pujos-Guillot (4) , Fabien Jourdan (5) , Franck Giacomoni (4) , Frédérique Courant (10, 10) , Gaelle Fave (1) , Gwenaëlle Le Gall (11) , Hubert Chassaigne (7) , Jean-Claude Tabet (12) , Jean-Francois Martin (4) , Jean-Philippe Antignac (10) , Laetitia Shintu (13) , Marianne Defernez , Mark Philo (11) , Marie-Cécile Alexandre Gouaubau (13) , Marie Josephe Amiot-Carlin (1) , Mathilde Bossis (7) , Mohamed Triba (14) , Nathali Stojilkovic (15) , Nathalie Banzet , Roland Molinié (16) , Romain Bott (1) , Sophie Goulitquer (17) , Stefano Caldarelli (13) , Douglas Rutledge (9)

1 NORT - Nutrition, obésité et risque thrombotique
2 SPO - Sciences Pour l'Oenologie
3 bruker
4 UNH - Unité de Nutrition Humaine
5 UTA - Toxicologie Alimentaire
6 SPI - Service de Pharmacologie et Immunoanalyse
7 Institute for Health and Consumer Protection
8 BFP - Biologie du fruit et pathologie
9 GENIAL - Ingénierie Procédés Aliments
10 LABERCA - Laboratoire d'étude des Résidus et Contaminants dans les Aliments
11 Norwich Research Park
12 IPCM - Institut Parisien de Chimie Moléculaire
13 ISM2 - Institut des Sciences Moléculaires de Marseille
14 CSPBAT - Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques
15 LCH - Laboratoire des Courses Hippiques
16 BIOPI - Biologie des Plantes et Innovation - UR UPJV 3900
17 SBR - Station biologique de Roscoff [Roscoff]

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 inhouse 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.

Mots clés: Inter-laboratory; Untargeted metabolomics; Mass spectrometry; Nuclear magnetic resonance; Metabolic fingerprinting

Domaines: Alimentation et Nutrition

Jean-Charles Martin, Mathieu Maillot, Gerard Mazerolles, Alexandre Verdu, Bernard Lyan, et al.. Can we Trust Untargeted Metabolomics: Results of the Metabo-ring Initiative, a Large-scale Multi-instruments Inter-laboratoire Study. 9. Annual Conference of the Metabolomics Society, Jul 2013, Glasgow, United Kingdom. 2013, 9th Annual Conference of the Metabolomics Society. ⟨hal-01123136⟩