title: Discovering Regulated Metabolite Families in Untargeted Metabolomics Studies.
abstract: The identification of metabolites by mass spectrometry constitutes a major bottleneck which considerably limits the throughput of metabolomics studies in biomedical or plant research. Here, we present a novel approach to analyze metabolomics data from untargeted, data-independent LC-MS/MS measurements. By integrated analysis of MS(1) abundances and MS/MS spectra, the identification of regulated metabolite families is achieved. This approach offers a global view on metabolic regulation in comparative metabolomics. We implemented our approach in the web application "MetFamily", which is freely available at http://msbi.ipb-halle.de/MetFamily/ . MetFamily provides a dynamic link between the patterns based on MS(1)-signal intensity and the corresponding structural similarity at the MS/MS level. Structurally related metabolites are annotated as metabolite families based on a hierarchical cluster analysis of measured MS/MS spectra. Joint examination with principal component analysis of MS(1) patterns, where this annotation is preserved in the loadings, facilitates the interpretation of comparative metabolomics data at the level of metabolite families. As a proof of concept, we identified two trichome-specific metabolite families from wild-type tomato Solanum habrochaites LA1777 in a fully unsupervised manner and validated our findings based on earlier publications and with NMR.
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Stress and Developmental Biology, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Treutler
authors.affiliation: RIKEN Center for Sustainable Resource Science , Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsugawa
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzel
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Stress and Developmental Biology, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Gorzolka
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Cell and Metabolic Biology, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Alain
authors.initials: A
authors.lastname: Tissier
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Stress and Developmental Biology, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Leibniz Institute of Plant Biochemistry , Department of Cell and Metabolic Biology, Weinberg 3, D-06120 Halle/Saale, Germany.
authors.forename: Gerd Ulrich
authors.initials: GU
authors.lastname: Balcke
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D018551:Solanum lycopersicum / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D018515:Plant Leaves / Q000378:metabolism; D025341:Principal Component Analysis; D053719:Tandem Mass Spectrometry; D014584:User-Computer Interface