Systematic Evaluation of Normalization Methods for Glycomics Data Based on Performance of Network Inference
Metabolites, vol. 10, pp. 271
Abstract
Glycomics measurements, like all other high-throughput technologies, are subject to technical variation due to fluctuations in the experimental conditions. The removal of this non-biological signal from the data is referred to as normalization. Contrary to other omics data types, a systematic evaluation of normalization options for glycomics data has not been published so far. In this paper, we assess the quality of different normalization strategies for glycomics data with an innovative approach. It has been shown previously that Gaussian Graphical Models (GGMs) inferred from glycomics data are able to identify enzymatic steps in the glycan synthesis pathways in a data-driven fashion. Based on this finding, here, we quantify the quality of a given normalization method according to how well a GGM inferred from the respective normalized data reconstructs known synthesis reactions in the glycosylation pathway. The method therefore exploits a biological measure of goodness. We analyzed 23 different normalization combinations applied to six large-scale glycomics cohorts across three experimental platforms: Liquid Chromatography - ElectroSpray Ionization - Mass Spectrometry (LC-ESI-MS), Ultra High Performance Liquid Chromatography with Fluorescence Detection (UHPLC-FLD), and Matrix Assisted Laser Desorption Ionization - Furier Transform Ion Cyclotron Resonance - Mass Spectrometry (MALDI-FTICR-MS). Based on our results, we recommend normalizing glycan data using the 'Probabilistic Quotient' method followed by log-transformation, irrespective of the measurement platform. This recommendation is further supported by an additional analysis, where we ranked normalization methods based on their statistical associations with age, a factor known to associate with glycomics measurements.
Authors 17
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Helmholtz Munich · Weill Cornell Medicine · Institute of Computational Biology
Affiliation as printed
Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10022, USA
Institute of Computational Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
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Helmholtz Munich · Max Planck Institute of Psychiatry · Institute of Computational Biology
Affiliation as printed
Institute of Computational Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Max Planck Institute for Psychiatry, 80804 Munich, Germany
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Affiliation as printed
Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia
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Affiliation as printed
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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Utrecht University · Leiden University Medical Center
Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 CH Utrecht, The Netherlands
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
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L. Renee Ruhaak Aachen Center for Proteomics and Metabolomics Department of Clinical Chemistry Laboratory Medicine
Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
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Affiliation as printed
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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Affiliation as printed
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 CH Utrecht, The Netherlands
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Affiliation as printed
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
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Gen-info · University of Split
Affiliation as printed
Gen-Info Ltd., 10000 Zagreb, Croatia
Medical School, University of Split, 21000 Split, Croatia
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Institute of Genetics and Cancer · MRC Human Genetics Unit · University of Edinburgh
Affiliation as printed
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
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Leiden University Medical Center
Affiliation as printed
Section of Molecular Epidemiology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Section of Molecular Epidemiology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
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Institute of Genetics and Cancer · MRC Human Genetics Unit · University of Edinburgh
Affiliation as printed
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh EH8 9YL, UK
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Affiliation as printed
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia
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Jan Krumsiek corresponding
Helmholtz Munich · Weill Cornell Medicine · Institute of Computational Biology
Affiliation as printed
Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10022, USA
Institute of Computational Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
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