Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study
Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study
ABSTRACT BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in type 2 diabetes (T2D) and beyond. Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and ultimately hepatocellular carcinomas. Methods and FindingsUtilizing the baseline data from the IMI DIRECT participants (n=1514) we sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Multi-omic (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, and measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI image-derived liver fat content (<5% or ≥5%). We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and Random Forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operator characteristic area under the curve (ROCAUC) of 0.84 (95% confidence interval (CI)=0.82, 0.86), which compared with a ROCAUC of 0.82 (95% CI=0.81, 0.83) for a model including nine clinically-accessible variables. The IMI DIRECT prediction models out-performed existing non-invasive NAFLD prediction tools. ConclusionsWe have developed clinically useful liver fat prediction models (see: www.predictliverfat.org) and identified biological features that appear to affect liver fat accumulation.
McDonald Timothy J、Haid Mark、Pavo Imre、Fitipaldi Hugo、Fernandez Juan、Dawed Adem Y、Forgie Ian M、Rutters Femke、Chabanova Elizaveta、Dale Matilda、De Masi Federico、Pedersen Helle Krogh、Raverdy Violeta、H?ussler Ragna S、Thomsen Henrik S、Vestergaard Henrik、Brunak S?ren、Beulens Joline WJ、??t Hart Leen M、Frost Gary、Hansen Torben、Pomares-Millan Hugo、Atabaki-Pasdar Naeimeh、Vi?uela Ana、Thomas E Louise、Elders Petra JM、Brage Soren、Mahajan Anubha、Kurbasic Azra、Allin Kristine H、Ruetten Hartmut、Musholt Petra B、Franks Paul W、Vangipurapu Jagadish、Laakso Markku、Mari Andrea、Jones Angus G、Schwenk Jochen M、Hattersley Andrew T、McCarthy Mark I、Pattou Francois、Pearson Ewan R、Frau Francesca、Hansen Tue H、Kennedy Gwen、Adamski Jerzy、Cederberg Henna、McEvoy Donna、Mutie Pascal M、Hong Mun-Gwan、Walker Mark、Bell Jimmy D、Kokkola Tarja、Giordano Giuseppe N、Thomas Cecilia Engel、Ohlsson Mattias、Heggie Alison、Gupta Ramneek、Sharma Sapna、Ridderstr?le Martin、Dermitzakis Emmanouil、Pedersen Oluf、Koivula Robert W
The Institute of Clinical and Biological Sciences, University of Exeter College of Medicine and Health, University of Exeter||Blood Sciences, Royal Devon and Exeter NHS Foundation TrustResearch Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthEli Lilly Regional Operations GmbHGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityPopulation Health & Genomics, School of Medicine, University of Dundee, Ninewells HospitalPopulation Health & Genomics, School of Medicine, University of Dundee, Ninewells HospitalAmsterdam UMC, location VUmc, Department of Epidemiology and Biostatistics, Amsterdam Public Health research instituteDepartment of Diagnostic Radiology, Copenhagen University Hospital Herlev GentofteAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of TechnologyDepartment of Health Technology, Technical University of DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenUniversity of Lille, Inserm, UMR 1190, Translational Research in DiabetesAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of TechnologyDepartment of Diagnostic Radiology, Copenhagen University Hospital Herlev GentofteNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Steno Diabetes Center CopenhagenDepartment of Health Technology, Technical University of Denmark||Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenAmsterdam UMC, location VUmc, Department of Epidemiology and Biostatistics, Amsterdam Public Health research institute||Julius Center for Health Sciences and Primary Care, University Medical Center UtrechtAmsterdam UMC, location VUmc, Department of Epidemiology and Biostatistics, Amsterdam Public Health research institute||Department of Cell and Chemical Biology, Leiden University Medical Center||Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical CenterSection for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Imperial College Hammersmith CampusNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Faculty of Health Sciences, University of Southern DenmarkGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityDepartment of Genetic Medicine and Development, University of Geneva Medical School||Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva Medical School||Swiss Institute of BioinformaticsResearch Centre for Optimal Health, School of Life Sciences, University of WestminsterDepartment of General Practice, Amsterdam UMC ¨C location VUmc, Amsterdam Public Health research instituteMRC Epidemiology Unit, University of CambridgeWellcome Centre for Human Genetics, University of OxfordGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg HospitalSanofi-Aventis Deutschland GmbHSanofi, Diabetes Division, Research and DevelopmentGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University||Department of Nutrition, Harvard School of Public Health||Department of Public Health & Clinical Medicine, Section for Medicine, Ume? UniversityInstitute of Clinical Medicine, Internal Medicine, University of Eastern FinlandInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland||Department of Medicine, University of Eastern Finland and Kuopio University HospitalInstitute of Neuroscience, National Research CouncilThe Institute of Clinical and Biological Sciences, University of Exeter College of Medicine and Health, University of ExeterAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of TechnologyThe Institute of Clinical and Biological Sciences, University of Exeter College of Medicine and Health, University of ExeterOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford||Wellcome Centre for Human Genetics, University of Oxford||Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital||OMNI Human Genetics, GenentechUniversity of Lille, Inserm, UMR 1190, Translational Research in DiabetesPopulation Health & Genomics, School of Medicine, University of Dundee, Ninewells HospitalSanofi-Aventis Deutschland GmbHNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Department of Cardiology and Endocrinology, Slagelse HospitalThe Immunoassay Biomarker Core Laboratory, School of Medicine, University of Dundee, Ninewells HospitalResearch Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Lehrstuhl f¨1r Experimentelle Genetik, Technische Universit?t M¨1nchen||Department of Biochemistry, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Endocrinology, Abdominal Centre, Helsinki University HospitalInstitute of Cellular Medicine (Diabetes), Newcastle UniversityGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of TechnologyInstitute of Cellular Medicine (Diabetes), Newcastle UniversityResearch Centre for Optimal Health, School of Life Sciences, University of WestminsterInstitute of Clinical Medicine, Internal Medicine, University of Eastern FinlandGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund UniversityAffinity Proteomics, Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of TechnologyDepartment of Astronomy and Theoretical Physics, Computational Biology and Biological Physics Unit, Lund University||Center for Applied Intelligent Systems Research, Halmstad UniversityInstitute of Cellular Medicine (Diabetes), Newcastle UniversityDepartment of Health Technology, Technical University of DenmarkGerman Center for Diabetes Research||Unit of Molecular Epidemiology, Institute of Epidemiology IIClinical Pharmacology and Translational MedicineDepartment of Genetic Medicine and Development, University of Geneva Medical School||Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva Medical School||Swiss Institute of BioinformaticsNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenGenetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University||Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford
医学研究方法基础医学预防医学
McDonald Timothy J,Haid Mark,Pavo Imre,Fitipaldi Hugo,Fernandez Juan,Dawed Adem Y,Forgie Ian M,Rutters Femke,Chabanova Elizaveta,Dale Matilda,De Masi Federico,Pedersen Helle Krogh,Raverdy Violeta,H?ussler Ragna S,Thomsen Henrik S,Vestergaard Henrik,Brunak S?ren,Beulens Joline WJ,??t Hart Leen M,Frost Gary,Hansen Torben,Pomares-Millan Hugo,Atabaki-Pasdar Naeimeh,Vi?uela Ana,Thomas E Louise,Elders Petra JM,Brage Soren,Mahajan Anubha,Kurbasic Azra,Allin Kristine H,Ruetten Hartmut,Musholt Petra B,Franks Paul W,Vangipurapu Jagadish,Laakso Markku,Mari Andrea,Jones Angus G,Schwenk Jochen M,Hattersley Andrew T,McCarthy Mark I,Pattou Francois,Pearson Ewan R,Frau Francesca,Hansen Tue H,Kennedy Gwen,Adamski Jerzy,Cederberg Henna,McEvoy Donna,Mutie Pascal M,Hong Mun-Gwan,Walker Mark,Bell Jimmy D,Kokkola Tarja,Giordano Giuseppe N,Thomas Cecilia Engel,Ohlsson Mattias,Heggie Alison,Gupta Ramneek,Sharma Sapna,Ridderstr?le Martin,Dermitzakis Emmanouil,Pedersen Oluf,Koivula Robert W.Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study[EB/OL].(2025-03-28)[2025-05-02].https://www.medrxiv.org/content/10.1101/2020.02.10.20021147.点此复制
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