title: Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology.
abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p-value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-α-acetyl-l-arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population.
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.
authors.forename: Binta
authors.initials: B
authors.lastname: Diémé
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mavel
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.|Service de Biochimie Et Biologie Moléculaire, Centre Hospitalier Régional Universitaire (CHRU) de Tours , 37044 Tours, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.affiliation: Service de Pédopsychiatrie, CHRU de Tours , 37044 Tours, France.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Tripi
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.|Service de Pédopsychiatrie, CHRU de Tours , 37044 Tours, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bonnet-Brilhault
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.|Service de Pédopsychiatrie, CHRU de Tours , 37044 Tours, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Malvy
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bocca
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.|Service de Biochimie Et Biologie Moléculaire, Centre Hospitalier Régional Universitaire (CHRU) de Tours , 37044 Tours, France.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Nadal-Desbarats
authors.affiliation: INSERM U930, Imagerie et Cerveau, Université François-Rabelais , 37000 Tours, France.|Service de Biochimie Et Biologie Moléculaire, Centre Hospitalier Régional Universitaire (CHRU) de Tours , 37044 Tours, France.|Service de Médecine Nucléaire In Vitro, CHRU de Tours , 37044 Tours, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
mesh_terms: D000293:Adolescent; D000596:Amino Acids / Q000378:metabolism; D000067877:Autism Spectrum Disorder / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods* / Q000706:statistics & numerical data; D015999:Multivariate Analysis; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000596:Amino Acids; D015415:Biomarkers
keywords: ASD; LC−HRMS; NMR; autism spectrum disorder; data fusion; metabolomics