Bayesian network imputation methods applied to multi-omics data identify putative causal relationships in a type 2 diabetes dataset containing incomplete data: An IMI DIRECT Study
PLoS Genetics, vol. 21, pp. e1011776
Abstract
Here we report the results from exploratory analysis using a Bayesian network approach of data originally derived from a large North European study of type 2 diabetes (T2D) conducted by the IMI DIRECT consortium. 3029 individuals (795 with T2D and 2234 without) within 7 different study centres provided data comprising genotypes, proteins, metabolites, gene expression measurements and many different clinical variables. The main aim of the current study was to demonstrate the utility of our previously developed method to fit Bayesian networks by performing exploratory analysis of this dataset to identify possible causal relationships between these variables. The data was analysed using the BayesNetty software package, which can handle mixed discrete/continuous data with missing values. The original dataset consisted of over 16,000 variables, which were filtered down to 260 variables for analysis. Even with this reduction, no individual had complete data for all variables, making it impossible to analyse using standard Bayesian network methodology. However, using the recently proposed novel imputation method implemented in BayesNetty we computed a large average Bayesian network from which we could infer possible associations and causal relationships between variables of interest. Our results confirmed many previous findings in connection with T2D, including possible mediating proteins and genes, some of which have not been widely reported. We also confirmed potential causal relationships with liver fat that were identified in an earlier study that used the IMI DIRECT dataset but was limited to a smaller subset of individuals and variables (namely individuals with complete data at pre-defined variables of interest). In addition to providing valuable confirmation, our analyses thus demonstrate a proof-of-principle of the utility of the method implemented within BayesNetty. The full final average Bayesian network generated from our analysis is freely available and can be easily interrogated further to address specific focussed scientific questions of interest.
Authors 38
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Affiliation as printed
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
Research Software Engineering, Newcastle University, Newcastle upon Tyne, United Kingdom
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Affiliation as printed
Research Unit of Molecular Epidemiology, Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, München, Germany
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University of Ljubljana · National University of Singapore · Helmholtz Munich
Affiliation as printed
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Institute of Experimental Genetics, German Research Center for Environmental Health, Helmholtz Zentrum München, München, Germany
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University of Copenhagen · Lund University · University of Oxford · Oxford Centre for Diabetes, Endocrinology and Metabolism · Novo Nordisk Foundation Center for Basic Metabolic Research
Affiliation as printed
Department of Clinical Science, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Lund, Sweden
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
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University of Copenhagen · Novo Nordisk Foundation
Affiliation as printed
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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University of Copenhagen · Novo Nordisk Foundation
Affiliation as printed
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Technical University of Denmark
Affiliation as printed
Department of Health Technology, Technical University of Denmark, Lyngby, Denmark
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Affiliation as printed
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
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Centre for Human Genetics · University of Oxford
Affiliation as printed
Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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University of Dundee · Ninewells Hospital
Affiliation as printed
Diabetes Endocrinology and Reproductive Biology, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
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Queen Mary University of London · Lund University
Affiliation as printed
Department of Clinical Science, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Lund, Sweden
Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom
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Affiliation as printed
Department of Clinical Science, Genetic and Molecular Epidemiology, Lund University Diabetes Centre, Lund, Sweden
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Affiliation as printed
Metabolomics and Proteomics Core, German Research Center for Environmental Health, Helmholtz Zentrum München, München, Germany
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University of Copenhagen · Zealand University Hospital Køge · Novo Nordisk Foundation Center for Basic Metabolic Research
Affiliation as printed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Medical Department, Zealand University Hospital, Køge, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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University of Copenhagen · Zealand University Hospital Køge · Novo Nordisk Foundation Center for Basic Metabolic Research
Affiliation as printed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Medical Department, Zealand University Hospital, Køge, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Amsterdam University Medical Centers
Affiliation as printed
Department of General Practice Medicine, Amsterdam UMC, Amsterdam, The Netherlands
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University of Exeter · Royal Devon University Healthcare NHS Foundation Trust
Affiliation as printed
Department of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, United Kingdom
Macleod Diabetes and Endocrine Centre, Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom
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Science for Life Laboratory · KTH Royal Institute of Technology
Affiliation as printed
SciLifeLab, Department of Protein Science, KTH - Royal Institute of Technology, Stockholm, Sweden
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University of Copenhagen · Novo Nordisk Foundation
Affiliation as printed
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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University of Exeter · Royal Devon University Healthcare NHS Foundation Trust
Affiliation as printed
Department of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, United Kingdom
Macleod Diabetes and Endocrine Centre, Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom
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University of Oxford · Oxford Centre for Diabetes, Endocrinology and Metabolism
Affiliation as printed
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
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Affiliation as printed
Internal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
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Centre for Human Genetics · University of Oxford
Affiliation as printed
Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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Affiliation as printed
Institute of Neuroscience, National Research Council, Rome, Italy
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Centre for Human Genetics · University of Oxford
Affiliation as printed
Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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University of Exeter · Royal Devon & Exeter NHS Foundation Trust · Royal Devon University Healthcare NHS Foundation Trust
Affiliation as printed
Academic Department of Clinical Biochemistry, Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom
Department of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, United Kingdom
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Affiliation as printed
Global Development, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
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Affiliation as printed
Eli Lilly Regional Operations GmbH, Wien, Austria
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University of Dundee · Ninewells Hospital
Affiliation as printed
Diabetes Endocrinology and Reproductive Biology, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
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University of Copenhagen · Gentofte Hospital · Novo Nordisk Foundation Center for Basic Metabolic Research
Affiliation as printed
Center for Clinical Metabolic Research, Herlev and Gentofte University Hospital, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Affiliation as printed
Sanofi Partnering, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
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Amsterdam University Medical Centers
Affiliation as printed
Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, The Netherlands
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Science for Life Laboratory · KTH Royal Institute of Technology
Affiliation as printed
SciLifeLab, Department of Protein Science, KTH - Royal Institute of Technology, Stockholm, Sweden
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Affiliation as printed
Research Unit of Molecular Epidemiology, Institute of Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, München, Germany
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Leiden University Medical Center · Amsterdam University Medical Centers
Affiliation as printed
Department of Cell and Chemical Biology, Leiden UMC, Leiden, The Netherlands
Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, The Netherlands
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University of Copenhagen · Novo Nordisk Foundation Center for Basic Metabolic Research · Steno Diabetes Center Copenhagen
Affiliation as printed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Copenhagen, Denmark
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University of Dundee · Ninewells Hospital · Newcastle University
Affiliation as printed
Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
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Heather Jane Cordell corresponding
Affiliation as printed
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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