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Discovery of drug–o...
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Allesøe, Rosa LundbyeNovo 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
(författare)
Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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2023-01-02
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Springer Nature,2023
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-330088
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-330088URI
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https://doi.org/10.1038/s41587-022-01520-xDOI
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https://lup.lub.lu.se/record/13c6b992-22aa-4bcc-b353-dbd6f2f72642URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Correction in DOI 10.1038/s41587-023-01805-9QC 20230626
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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.
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Lundgaard, Agnete TroenNovo 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
(författare)
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Hernández Medina, RicardoNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Aguayo-Orozco, AlejandroNovo 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
(författare)
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Johansen, JoachimNovo 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
(författare)
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Nissen, Jakob NyboNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Brorsson, CarolineNovo 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
(författare)
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Mazzoni, GianlucaNovo 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
(författare)
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Niu, LiliNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Biel, Jorge HernansanzNovo 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
(författare)
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Brasas, ValentasNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Webel, HenryNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Benros, Michael EriksenCopenhagen 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
(författare)
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Pedersen, Anders GormDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
(författare)
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Chmura, Piotr JaroslawNovo 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
(författare)
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Jacobsen, Ulrik PlesnerNovo 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
(författare)
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Mari, AndreaC.N.R. Institute of Neuroscience, Padova, Italy
(författare)
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Koivula, RobertWellcome Centre for Human Genetics, University of Oxford, Oxford, UK
(författare)
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Mahajan, AnubhaWellcome Centre for Human Genetics, University of Oxford, Oxford, UK
(författare)
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Vinuela, AnaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
(författare)
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Tajes, Juan FernandezWellcome Centre for Human Genetics, University of Oxford, Oxford, UK
(författare)
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Sharma, SapnaResearch 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
(författare)
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Haid, MarkMetabolomics and Proteomics Core, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany
(författare)
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Hong, Mun-GwanKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u19gmsru
(författare)
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Musholt, Petra B.Research and Development Global Development, Translational Medicine and Clinical Pharmacology, Sanofi-Aventis Deutschland, Frankfurt, Germany
(författare)
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De Masi, FedericoNovo 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
(författare)
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Vogt, JosefNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Pedersen, Helle KroghDepartment 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
(författare)
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Gudmundsdottir, ValborgNovo 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
(författare)
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Jones, AngusUniversity of Exeter Medical School, Exeter, UK
(författare)
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Kennedy, GwenThe Immunoassay Biomarker Core Laboratory, School of Medicine, University of Dundee, Dundee, UK
(författare)
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Bell, JimmyResearch Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK
(författare)
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Thomas, E. LouiseResearch Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK
(författare)
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Frost, GarySection for Nutrition Research, Faculty of Medicine, Imperial College London, London, UK
(författare)
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Thomsen, HenrikDepartment of Radiology, Copenhagen University Hospital Herlev-Gentofte, Herlev, Denmark
(författare)
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Hansen, ElizavetaDepartment of Radiology, Copenhagen University Hospital Herlev-Gentofte, Herlev, Denmark
(författare)
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Hansen, Tue HaldorNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Vestergaard, HenrikNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Ridderstråle, M.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-mri
(författare)
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Blom, Marieke T.Department of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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‘t Hart, Leen M.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
(författare)
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Pattou, FrancoisInserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France
(författare)
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Raverdy, VioletaInserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France
(författare)
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Brage, SorenMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
(författare)
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Kokkola, TarjaDepartment of Medicine, University of Eastern Finland, Kuopio, Finland
(författare)
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Heggie, AlisonInstitute of Cellular Medicine, Newcastle University, Newcastle, UK
(författare)
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McEvoy, DonnaDiabetes Research Network, Royal Victoria Infirmary, Newcastle, UK
(författare)
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Klintenberg, M.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-mk1
(författare)
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Kaye, JaneCentre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
(författare)
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Hattersley, AndrewUniversity of Exeter Medical School, Exeter, UK
(författare)
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McDonald, TimothyUniversity of Exeter Medical School, Exeter, UK
(författare)
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Ridderstråle, MartinLund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden
(författare)
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Walker, MarkTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
(författare)
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Forgie, IanDivision of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK
(författare)
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Giordano, G.N.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-geg
(författare)
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Pavo, ImreEli Lilly Regional Operations, Vienna, Austria
(författare)
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Ruetten, HartmutResearch and Development Global Development, Translational Medicine and Clinical Pharmacology, Sanofi-Aventis Deutschland, Frankfurt, Germany
(författare)
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Pedersen, OlufNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Hansen, TorbenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Dermitzakis, EmmanouilDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
(författare)
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Franks, P.W.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf
(författare)
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Schwenk, Jochen M.KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1h7wtme
(författare)
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Adamski, JerzyInstitute 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
(författare)
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McCarthy, Mark I.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
(författare)
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Pearson, EwanDivision of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK
(författare)
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Banasik, KarinaNovo 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
(författare)
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Rasmussen, SimonNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
(författare)
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Brunak, SørenNovo 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
(författare)
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Froguel, PhilippeInserm, Univ Lille, CHU Lille, Lille Pasteur Institute, EGID, Lille, France; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
(författare)
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Thomas, Cecilia EngelKTH,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(Swepub:kth)u1ja1scu
(författare)
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Häussler, Ragna S.KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1izv3pd
(författare)
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Beulens, JolineDepartment of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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Rutters, FemkeDepartment of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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Nijpels, GielDepartment of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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van Oort, SabineDepartment of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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Groeneveld, LenkaDepartment of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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Elders, PetraDepartment of General Practice, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
(författare)
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Giorgino, ToniBiophysics Institute (IBF-CNR), National Research Council of Italy, Milan, Italy; Department of Biosciences, University of Milan, Milan, Italy
(författare)
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Rodriquez, MarianneBiotech & Biomarkers Research Department, Institut de Recherches Internationales Servier, Croissy sur Seine, France
(författare)
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Nice, RachelBlood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
(författare)
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Perry, MandyBlood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
(författare)
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Bianzano, SusannaBoehringer Ingelheim International, Therapeutic Area CardioMetabolism and Respiratory Medicine, Ingelheim am Rhein, Germany
(författare)
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Graefe-Mody, UlrikeBoehringer Ingelheim International, Therapeutic Area CNS, Retinopathies and Emerging Areas, Ingelheim am Rhein, Germany
(författare)
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Hennige, AnitaBoehringer Ingelheim International, Medicine Cardiometabolism and Respiratory, Biberach an der Riss, Germany
(författare)
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Grempler, RolfBoehringer Ingelheim International, Translational Medicine & Clinical Pharmacology, Biberach an der Riss, Germany
(författare)
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Baum, PatrickBoehringer Ingelheim International, Translational Medicine & Clinical Pharmacology, Biberach an der Riss, Germany
(författare)
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Stærfeldt, Hans HenrikDepartment of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark
(författare)
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Shah, NishaCentre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
(författare)
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Teare, HarrietCentre for Health, Law and Emerging Technologies (HeLEX), Faculty of Law, University of Oxford, Oxford, UK
(författare)
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Ehrhardt, BeateCentre for Mathematics and Algorithms for Data, University of Bath, Bath, UK
(författare)
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Tillner, JoachimClinical Operations, Sanofi-Aventis Deutschland, Frankfurt, Germany
(författare)
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Dings, ChristianeClinical Pharmacy, Saarland University, Saarbrücken, Germany
(författare)
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Lehr, ThorstenClinical Pharmacy, Saarland University, Saarbrücken, Germany
(författare)
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Scherer, NinaClinical Pharmacy, Saarland University, Saarbrücken, Germany
(författare)
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Sihinevich, IrynaClinical Pharmacy, Saarland University, Saarbrücken, Germany
(författare)
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Cabrelli, LouiseClinical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK, Scotland
(författare)
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Loftus, HeatherClinical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK, Scotland
(författare)
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Bizzotto, RobertoC.N.R. Institute of Neuroscience, Padova, Italy
(författare)
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Tura, AndreaC.N.R. Institute of Neuroscience, Padova, Italy
(författare)
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Dekkers, KoenDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
(författare)
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Groop, L.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr
(författare)
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Pasdar, N.A.
(författare)
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Fitipaldi, H.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)hu3745fi
(författare)
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Kurbasic, A.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)mats-aku
(författare)
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Mutie, P.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)pa4264mu
(författare)
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Pomares-Millan, H.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)hu7454po
(författare)
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Abdalla, M.University of Oxford
(författare)
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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, DenmarkNovo 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
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Nature Biotechnology: Springer Nature41:3, s. 399-4081087-01561546-1696
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