Bioinformatics analysis of targeted metabolomics - uncovering old and new tales of diabetic mice under medication.

@article{citeulike:2622747, abstract = {Metabolomics is a powerful tool for identifying both known and new disease-related perturbations in metabolic pathways. In preclinical drug testing, it has a high potential for early identification of drug off-target effects. Recent advances in high-precision high-throughput mass spectrometry have brought the Metabolomics field to a point where quantitative, targeted, metabolomic measurements with ready-to-use kits allow for the automated in-house screening for hundreds of different metabolites in large sets of biological samples. Today, the field of metabolomics is, arguably, at a point where transcriptomics was about five years ago. This being so, the field has a strong need for adapted bioinformatics tools and methods. In this paper, we describe a systematic analysis of a targeted quantitative characterization of more than 800 metabolites in blood plasma samples from healthy and diabetic mice under rosiglitazone treatment. We show that known and new metabolic phenotypes of diabetes and medication can be recovered in a statistically objective manner. We find that concentrations of methylglutarylcarnitine are oppositely impacted by rosiglitazone treatment of both healthy and diabetic mice. Analyzing ratios between metabolite concentrations dramatically reduces the noise in the dataset, allowing for the discovery of new potential biomarkers of diabetes, such as the N-hydroxyacyloylsphingosyl-phosphocholines SM(OH)28:0 and SM(OH)26:0. Using a hierarchical clustering technique on partial eta-squared values, we identify functionally related groups of metabolites, indicating a diabetes-related shift from lysophosphatidylcholine to phosphatidylcholine levels. The bioinformatics data analysis approach introduced here can be readily generalized to other drug-testing scenarios and to other medical disorders.}, address = {Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum M\"{u}nchen, German Research Center for Environmental Health (GmbH), Ingolst\"{a}dter Landstrae 1,85764 Neuherberg, Germany; Biocrates life sciences AG, A-6020, Innsbruck, Austria; now at CSL Limited, Parkville, 45 Poplar Road, Parkville, VIC 3052, Australia; now at Institute for Bioinformatics, UMIT, A-6060 Hall in Tirol, Austria; Department of Genome-oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universit\"{a}t M\"{u}nchen, D-85350 Freising, Germany; Faculty of Biology, University of Munich (LMU), Grohaderner Strae 2, D-82152 Planegg-Martinsried, Germany.}, author = {Altmaier, Elisabeth and Ramsay, Steven L L. and Graber, Armin and Mewes, Hans-Werner W. and Weinberger, Klaus M M. and Suhre, Karsten }, citeulike-article-id = {2622747}, doi = {10.1210/en.2007-1747}, issn = {0013-7227}, journal = {Endocrinology}, month = {March}, posted-at = {2008-04-02 10:10:02}, priority = {2}, title = {Bioinformatics analysis of targeted metabolomics - uncovering old and new tales of diabetic mice under medication.}, url = {http://dx.doi.org/10.1210/en.2007-1747}, year = {2008} }

TY - JOUR ID - citeulike:2622747 L3 - citeulike-article-id:2622747 TI - Bioinformatics analysis of targeted metabolomics - uncovering old and new tales of diabetic mice under medication. JF - Endocrinology AD - Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstrae 1,85764 Neuherberg, Germany; Biocrates life sciences AG, A-6020, Innsbruck, Austria; now at CSL Limited, Parkville, 45 Poplar Road, Parkville, VIC 3052, Australia; now at Institute for Bioinformatics, UMIT, A-6060 Hall in Tirol, Austria; Department of Genome-oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität München, D-85350 Freising, Germany; Faculty of Biology, University of Munich (LMU), Grohaderner Strae 2, D-82152 Planegg-Martinsried, Germany. SN - 0013-7227 N2 - Metabolomics is a powerful tool for identifying both known and new disease-related perturbations in metabolic pathways. In preclinical drug testing, it has a high potential for early identification of drug off-target effects. Recent advances in high-precision high-throughput mass spectrometry have brought the Metabolomics field to a point where quantitative, targeted, metabolomic measurements with ready-to-use kits allow for the automated in-house screening for hundreds of different metabolites in large sets of biological samples. Today, the field of metabolomics is, arguably, at a point where transcriptomics was about five years ago. This being so, the field has a strong need for adapted bioinformatics tools and methods. In this paper, we describe a systematic analysis of a targeted quantitative characterization of more than 800 metabolites in blood plasma samples from healthy and diabetic mice under rosiglitazone treatment. We show that known and new metabolic phenotypes of diabetes and medication can be recovered in a statistically objective manner. We find that concentrations of methylglutarylcarnitine are oppositely impacted by rosiglitazone treatment of both healthy and diabetic mice. Analyzing ratios between metabolite concentrations dramatically reduces the noise in the dataset, allowing for the discovery of new potential biomarkers of diabetes, such as the N-hydroxyacyloylsphingosyl-phosphocholines SM(OH)28:0 and SM(OH)26:0. Using a hierarchical clustering technique on partial eta-squared values, we identify functionally related groups of metabolites, indicating a diabetes-related shift from lysophosphatidylcholine to phosphatidylcholine levels. The bioinformatics data analysis approach introduced here can be readily generalized to other drug-testing scenarios and to other medical disorders. AU - Altmaier, Elisabeth AU - Ramsay, Steven L AU - Graber, Armin AU - Mewes, Hans-Werner AU - Weinberger, Klaus M AU - Suhre, Karsten PY - 2008/03/27/ UR - http://dx.doi.org/10.1210/en.2007-1747 ER -