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Discovery of drug–o...
Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
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- Allesøe, Rosa Lundbye (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark; Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
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- Lundgaard, Agnete Troen (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Hernández Medina, Ricardo (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Aguayo-Orozco, Alejandro (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Johansen, Joachim (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Nissen, Jakob Nybo (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Brorsson, Caroline (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Mazzoni, Gianluca (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Niu, Lili (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Biel, Jorge Hernansanz (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Brasas, Valentas (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Webel, Henry (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Benros, Michael Eriksen (författare)
- Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Pedersen, Anders Gorm (författare)
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Chmura, Piotr Jaroslaw (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Jacobsen, Ulrik Plesner (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Mari, Andrea (författare)
- C.N.R. Institute of Neuroscience, Padova, Italy
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- Koivula, Robert (författare)
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
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- Mahajan, Anubha (författare)
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
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- Vinuela, Ana (författare)
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
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- Tajes, Juan Fernandez (författare)
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
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- Sharma, Sapna (författare)
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany, Bavaria; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany, Bavaria; Chair of Food Chemistry and Molecular and Sensory Science, Technical University of Munich, Freising, Germany
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- Haid, Mark (författare)
- Metabolomics and Proteomics Core, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany
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- Hong, Mun-Gwan (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
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- Musholt, Petra B. (författare)
- Research and Development Global Development, Translational Medicine and Clinical Pharmacology, Sanofi-Aventis Deutschland, Frankfurt, Germany
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- De Masi, Federico (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Vogt, Josef (författare)
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Pedersen, Helle Krogh (författare)
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Gudmundsdottir, Valborg (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Jones, Angus (författare)
- University of Exeter Medical School, Exeter, UK
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- Kennedy, Gwen (författare)
- The Immunoassay Biomarker Core Laboratory, School of Medicine, University of Dundee, Dundee, UK
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- Bell, Jimmy (författare)
- Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK
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- Thomas, E. Louise (författare)
- Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK
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- Frost, Gary (författare)
- Section for Nutrition Research, Faculty of Medicine, Imperial College London, London, UK
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- Thomsen, Henrik (författare)
- Department of Radiology, Copenhagen University Hospital Herlev-Gentofte, Herlev, Denmark
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- Hansen, Elizaveta (författare)
- Department of Radiology, Copenhagen University Hospital Herlev-Gentofte, Herlev, Denmark
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- Hansen, Tue Haldor (författare)
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Vestergaard, Henrik (författare)
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Ridderstråle, M. (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Blom, Marieke T. (författare)
- Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- ‘t Hart, Leen M. (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Biomedical Data Science, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
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- Pattou, Francois (författare)
- Inserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France
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- Raverdy, Violeta (författare)
- Inserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France
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- Brage, Soren (författare)
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
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- Kokkola, Tarja (författare)
- Department of Medicine, University of Eastern Finland, Kuopio, Finland
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- Heggie, Alison (författare)
- Institute of Cellular Medicine, Newcastle University, Newcastle, UK
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- McEvoy, Donna (författare)
- Diabetes Research Network, Royal Victoria Infirmary, Newcastle, UK
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- Klintenberg, M. (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Kaye, Jane (författare)
- Centre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
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- Hattersley, Andrew (författare)
- University of Exeter Medical School, Exeter, UK
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- McDonald, Timothy (författare)
- University of Exeter Medical School, Exeter, UK
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- Ridderstråle, Martin (författare)
- Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden
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- Walker, Mark (författare)
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
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- Forgie, Ian (författare)
- Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK
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- Giordano, G.N. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Pavo, Imre (författare)
- Eli Lilly Regional Operations, Vienna, Austria
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- Ruetten, Hartmut (författare)
- Research and Development Global Development, Translational Medicine and Clinical Pharmacology, Sanofi-Aventis Deutschland, Frankfurt, Germany
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- Pedersen, Oluf (författare)
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Hansen, Torben (författare)
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Dermitzakis, Emmanouil (författare)
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
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- Franks, P.W. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Schwenk, Jochen M. (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
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- Adamski, Jerzy (författare)
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; 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
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- McCarthy, Mark I. (författare)
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; Genentech, South San Francisco, CA, USA
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- Pearson, Ewan (författare)
- Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK
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- Banasik, Karina (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Rasmussen, Simon (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Brunak, Søren (författare)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Froguel, Philippe (författare)
- Inserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
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- Thomas, Cecilia Engel (författare)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Häussler, Ragna S. (författare)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
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- Beulens, Joline (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- Rutters, Femke (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- Nijpels, Giel (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- van Oort, Sabine (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- Groeneveld, Lenka (författare)
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- Elders, Petra (författare)
- Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
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- Giorgino, Toni (författare)
- Biophysics Institute (IBF-CNR), National Research Council of Italy, Milan, Italy; Department of Biosciences, University of Milan, Milan, Italy
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- Rodriquez, Marianne (författare)
- Biotech & Biomarkers Research Department, Institut de Recherches Internationales Servier, Croissy sur Seine, France
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- Nice, Rachel (författare)
- Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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- Perry, Mandy (författare)
- Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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- Bianzano, Susanna (författare)
- Boehringer Ingelheim International, Therapeutic Area CardioMetabolism and Respiratory Medicine, Ingelheim am Rhein, Germany
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- Graefe-Mody, Ulrike (författare)
- Boehringer Ingelheim International, Therapeutic Area CNS, Retinopathies and Emerging Areas, Ingelheim am Rhein, Germany
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- Hennige, Anita (författare)
- Boehringer Ingelheim International, Medicine Cardiometabolism and Respiratory, Biberach an der Riss, Germany
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- Grempler, Rolf (författare)
- Boehringer Ingelheim International, Translational Medicine & Clinical Pharmacology, Biberach an der Riss, Germany
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- Baum, Patrick (författare)
- Boehringer Ingelheim International, Translational Medicine & Clinical Pharmacology, Biberach an der Riss, Germany
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- Stærfeldt, Hans Henrik (författare)
- Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
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- Shah, Nisha (författare)
- Centre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
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- Teare, Harriet (författare)
- Centre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
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- Ehrhardt, Beate (författare)
- Centre for Mathematics and Algorithms for Data, University of Bath, Bath, UK
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- Tillner, Joachim (författare)
- Clinical Operations, Sanofi-Aventis Deutschland, Frankfurt, Germany
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- Dings, Christiane (författare)
- Clinical Pharmacy, Saarland University, Saarbrücken, Germany
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- Lehr, Thorsten (författare)
- Clinical Pharmacy, Saarland University, Saarbrücken, Germany
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- Scherer, Nina (författare)
- Clinical Pharmacy, Saarland University, Saarbrücken, Germany
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- Sihinevich, Iryna (författare)
- Clinical Pharmacy, Saarland University, Saarbrücken, Germany
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- Cabrelli, Louise (författare)
- Clinical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK, Scotland
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- Loftus, Heather (författare)
- Clinical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK, Scotland
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- Bizzotto, Roberto (författare)
- C.N.R. Institute of Neuroscience, Padova, Italy
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- Tura, Andrea (författare)
- C.N.R. Institute of Neuroscience, Padova, Italy
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- Dekkers, Koen (författare)
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
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- Groop, L. (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Pasdar, N.A. (författare)
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- Fitipaldi, H. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Kurbasic, A. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Mutie, P. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Pomares-Millan, H. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Abdalla, M. (författare)
- University of Oxford
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(creator_code:org_t)
- 2023-01-02
- 2023
- Engelska.
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
- Relaterad länk:
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https://doi.org/10.1...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
Ämnesord
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Deep learning
- Learning systems
- Patient treatment
- 'omics'
- Auto encoders
- In-silico
- Learning models
- Multi-modal data
- Multi-modal dataset
- Non-trivial tasks
- Omics technologies
- Phenotyping
- Type-2 diabetes
- Modal analysis
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Allesøe, Rosa Lu ...
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Lundgaard, Agnet ...
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Hernández Medina ...
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Aguayo-Orozco, A ...
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Johansen, Joachi ...
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Nissen, Jakob Ny ...
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Brorsson, Caroli ...
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Mazzoni, Gianluc ...
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Niu, Lili
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Biel, Jorge Hern ...
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Brasas, Valentas
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Webel, Henry
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Benros, Michael ...
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Pedersen, Anders ...
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Chmura, Piotr Ja ...
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Jacobsen, Ulrik ...
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Mari, Andrea
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Koivula, Robert
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Mahajan, Anubha
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Vinuela, Ana
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Tajes, Juan Fern ...
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Sharma, Sapna
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Haid, Mark
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Hong, Mun-Gwan
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Musholt, Petra B ...
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De Masi, Federic ...
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Vogt, Josef
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Pedersen, Helle ...
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Gudmundsdottir, ...
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Jones, Angus
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Kennedy, Gwen
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Bell, Jimmy
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Thomas, E. Louis ...
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Frost, Gary
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Thomsen, Henrik
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Hansen, Elizavet ...
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Hansen, Tue Hald ...
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Vestergaard, Hen ...
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Ridderstråle, M.
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Blom, Marieke T.
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‘t Hart, Leen M.
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Pattou, Francois
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Raverdy, Violeta
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Brage, Soren
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Kokkola, Tarja
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Heggie, Alison
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McEvoy, Donna
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Klintenberg, M.
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Kaye, Jane
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Hattersley, Andr ...
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McDonald, Timoth ...
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Ridderstråle, Ma ...
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Walker, Mark
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Forgie, Ian
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Giordano, G.N.
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Pavo, Imre
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Ruetten, Hartmut
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Pedersen, Oluf
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Hansen, Torben
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Dermitzakis, Emm ...
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Franks, P.W.
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Schwenk, Jochen ...
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Adamski, Jerzy
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McCarthy, Mark I ...
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Pearson, Ewan
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Banasik, Karina
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Rasmussen, Simon
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Brunak, Søren
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Froguel, Philipp ...
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Thomas, Cecilia ...
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Häussler, Ragna ...
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Beulens, Joline
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Rutters, Femke
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Nijpels, Giel
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van Oort, Sabine
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Groeneveld, Lenk ...
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Elders, Petra
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Giorgino, Toni
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Rodriquez, Maria ...
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Nice, Rachel
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Perry, Mandy
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Bianzano, Susann ...
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Graefe-Mody, Ulr ...
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Hennige, Anita
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Grempler, Rolf
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Baum, Patrick
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Stærfeldt, Hans ...
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Shah, Nisha
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Teare, Harriet
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Ehrhardt, Beate
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Tillner, Joachim
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Dings, Christian ...
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Lehr, Thorsten
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Scherer, Nina
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Sihinevich, Iryn ...
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Cabrelli, Louise
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Loftus, Heather
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Bizzotto, Robert ...
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Tura, Andrea
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Dekkers, Koen
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Groop, L.
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Pasdar, N.A.
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Fitipaldi, H.
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Kurbasic, A.
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Mutie, P.
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Pomares-Millan, ...
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Abdalla, M.
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MEDICIN OCH HÄLS ...
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