title: Optimization of a liquid chromatography ion mobility-mass spectrometry method for untargeted metabolomics using experimental design and multivariate data analysis.
abstract: High-resolution mass spectrometry coupled with pattern recognition techniques is an established tool to perform comprehensive metabolite profiling of biological datasets. This paves the way for new, powerful and innovative diagnostic approaches in the post-genomic era and molecular medicine. However, interpreting untargeted metabolomic data requires robust, reproducible and reliable analytical methods to translate results into biologically relevant and actionable knowledge. The analyses of biological samples were developed based on ultra-high performance liquid chromatography (UHPLC) coupled to ion mobility - mass spectrometry (IM-MS). A strategy for optimizing the analytical conditions for untargeted UHPLC-IM-MS methods is proposed using an experimental design approach. Optimization experiments were conducted through a screening process designed to identify the factors that have significant effects on the selected responses (total number of peaks and number of reliable peaks). For this purpose, full and fractional factorial designs were used while partial least squares regression was used for experimental design modeling and optimization of parameter values. The total number of peaks yielded the best predictive model and is used for optimization of parameters setting.
authors.affiliation: Normandie Univ, COBRA, UMR 6014 and FR 3038, Université de Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France; Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen, France; Department of Metabolic Biochemistry, Rouen University Hospital, Rouen, France. Electronic address: abdellah.tebani@chu-rouen.fr.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Tebani
authors.affiliation: Normandie Univ, COBRA, UMR 6014 and FR 3038, Université de Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schmitz-Afonso
authors.affiliation: UMR Genial, AgroParisTech, INRA, Université Paris-Saclay, 91300, Massy, France.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Rutledge
authors.affiliation: Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen, France.
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Gonzalez
authors.affiliation: Region-Inserm Team NeoVasc ERI28, Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Institute of Research for Innovation in Biomedicine, Normandy University, Rouen, France; Department of Metabolic Biochemistry, Rouen University Hospital, Rouen, France.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
authors.affiliation: Normandie Univ, COBRA, UMR 6014 and FR 3038, Université de Rouen, INSA Rouen, CNRS, IRCOF, 1 Rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France. Electronic address: carlos.afonso@univ-rouen.fr.
authors.forename: Carlos
authors.initials: C
authors.lastname: Afonso
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics; D015999:Multivariate Analysis
keywords: Chemometrics; Experimental design; Ion mobility; Mass spectrometry; Metabolomics