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Combinatorial, addi...
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Forslund, Sofia K.European Molecular Biology Laboratory
(author)
Combinatorial, additive and dose-dependent drug–microbiome associations
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-12-08
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Springer Science and Business Media LLC,2021
Numbers
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LIBRIS-ID:oai:research.chalmers.se:da6b8b1e-2ec9-4f0a-8cf3-e37a7def8d88
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https://research.chalmers.se/publication/527761URI
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https://doi.org/10.1038/s41586-021-04177-9DOI
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https://gup.ub.gu.se/publication/311770URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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Chakaroun, RimaUniversität Leipzig,Leipzig University
(author)
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Zimmermann-Kogadeeva, MariaEuropean Molecular Biology Laboratory
(author)
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Markó, LajosMax Delbrueck Centrum Fuer Molekulare Medizin,The Max Delbrück Center for Molecular Medicine
(author)
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Aron-Wisnewsky, Judith
(author)
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Nielsen, TrineKöpenhamns universitet,University of Copenhagen
(author)
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Moitinho-Silva, LucasEuropean Molecular Biology Laboratory
(author)
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Schmidt, Thomas S. B.European Molecular Biology Laboratory
(author)
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Falony, GwenKatholieke Universiteit Leuven
(author)
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Vieira-Silva, SaraKatholieke Universiteit Leuven
(author)
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Adriouch, Solia
(author)
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Alves, RenatoEuropean Molecular Biology Laboratory
(author)
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Assmann, Karen
(author)
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Bastard, Jean-PhillippeAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Birkner, TillMax Delbrueck Centrum Fuer Molekulare Medizin,The Max Delbrück Center for Molecular Medicine
(author)
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Caesar, Robert,1973Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Center for Cardiovascular and Metabolic Research (CMR),Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcaero
(author)
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Chilloux, J.Imperial College of Science, Technology and Medicine
(author)
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Coelho, Luis P.European Molecular Biology Laboratory
(author)
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Fezeu, Leopold
(author)
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Galleron, NathalieUniversité Paris-Saclay,University Paris-Saclay
(author)
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Helft, GerardAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Isnard, RichardAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Ji, Boyang,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)bojand
(author)
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Kuhn, MichaelEuropean Molecular Biology Laboratory
(author)
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Le Chatelier, EmmanuelleUniversité Paris-Saclay,University Paris-Saclay
(author)
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Myridakis, AntonisImperial College of Science, Technology and Medicine
(author)
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Olsson, Lisa M.,1984Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xollit
(author)
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Pons, NicolasUniversité Paris-Saclay,University Paris-Saclay
(author)
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Prifti, Edi
(author)
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Quinquis, BenoitUniversité Paris-Saclay,University Paris-Saclay
(author)
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Roume, HugoUniversité Paris-Saclay,University Paris-Saclay
(author)
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Salem, Joe-Elie
(author)
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Sokolovska, Nataliya
(author)
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Tremaroli, Valentina,1978Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Center for Cardiovascular and Metabolic Research (CMR),Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xtreva
(author)
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Vallès-Colomer, MireiaKatholieke Universiteit Leuven
(author)
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Lewinter, ChristianKöpenhamns universitet,University of Copenhagen
(author)
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Søndertoft, Nadja B.Köpenhamns universitet,University of Copenhagen
(author)
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Pedersen, Helle K.Köpenhamns universitet,University of Copenhagen
(author)
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Hansen, Tue H.Köpenhamns universitet,University of Copenhagen
(author)
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Amouyal, Chloe
(author)
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Andersson Galijatovic, Ehm AstridKöpenhamns universitet,University of Copenhagen
(author)
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Andreelli, Fabrizio
(author)
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Barthelemy, OlivierAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Batisse, Jean-PaulAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Belda, EugeniAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Berland, MagalieUniversité Paris-Saclay,University Paris-Saclay
(author)
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Bittar, RandaAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Blottière, HervéUniversité Paris-Saclay,University Paris-Saclay
(author)
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Bosquet, FredericBiobyte Solutions GmbH
(author)
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Boubrit, RachidAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Bourron, OlivierBiobyte Solutions GmbH
(author)
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Camus, MickaelUniversité Paris-Saclay,University Paris-Saclay
(author)
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Cassuto, DominiqueAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Ciangura, CecileAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Collet, Jean-PhilippeAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Dao, Maria-Carlota
(author)
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Djebbar, MoradAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Doré, AngéliqueUniversité Paris-Saclay,University Paris-Saclay
(author)
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Engelbrechtsen, Line
(author)
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Fellahi, SorayaAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Fromentin, SebastienUniversité Paris-Saclay,University Paris-Saclay
(author)
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Galan, PilarImperial College of Science, Technology and Medicine
(author)
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Gauguier, DominiqueMcGill University
(author)
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Giral, PhilippeAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Hartemann, AgnesBiobyte Solutions GmbH
(author)
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Hartmann, BoletteKöpenhamns universitet,University of Copenhagen
(author)
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Holst, Jens JuulKöpenhamns universitet,University of Copenhagen
(author)
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Hornbak, MaleneKöpenhamns universitet,University of Copenhagen
(author)
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Hoyles, L.Nottingham Trent University
(author)
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Hulot, Jean-Sébastien
(author)
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Jaqueminet, SophieUniversité Paris-Saclay,University Paris-Saclay
(author)
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Jørgensen, Niklas RyeBiobyte Solutions GmbH
(author)
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Julienne, HannaUniversité Paris-Saclay,University Paris-Saclay
(author)
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Justesen, JohanneKöpenhamns universitet,University of Copenhagen
(author)
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Kammer, JudithUniversität Leipzig,Leipzig University
(author)
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Krarup, NikolajKöpenhamns universitet,University of Copenhagen
(author)
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Kerneis, MathieuAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Khemis, JeanAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Kozlowski, RubyImperial College of Science, Technology and Medicine
(author)
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Lejard, VéroniqueAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Levenez, FlorenceAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Lucas-Martini, LeaAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Massey, RobinAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Martinez-Gili, Laura
(author)
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Maziers, NicolasUniversité Paris-Saclay,University Paris-Saclay
(author)
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Medina-Stamminger, JonathanAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Montalescot, GillesAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Moute, Sandrine
(author)
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Neves, Ana LuisaImperial College of Science, Technology and Medicine
(author)
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Olanipekun, MichaelImperial College of Science, Technology and Medicine
(author)
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Le Pavin, Laetitia PaseroUniversité Paris-Saclay,University Paris-Saclay
(author)
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Poitou, Christine
(author)
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Pousset, FrancoiseAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Pouzoulet, LaurenceAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Rodriguez-Martinez, AndreaImperial College of Science, Technology and Medicine
(author)
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Rouault, Christine
(author)
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Silvain, JohanneAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Svendstrup, MathildeKöpenhamns universitet,University of Copenhagen
(author)
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Swartz, Timothy
(author)
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Vanduyvenboden, ThierryUniversité Paris-Saclay,University Paris-Saclay
(author)
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Vatier, CamilleAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Walther, StefanieUniversität Leipzig,Leipzig University
(author)
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Gøtze, Jens P.Köpenhamns universitet,University of Copenhagen
(author)
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Køber, LarsKöpenhamns universitet,University of Copenhagen
(author)
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Vestergaard, H.Köpenhamns universitet,University of Copenhagen
(author)
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Hansen, TorbenKöpenhamns universitet,University of Copenhagen
(author)
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Zucker, Jean-Daniel
(author)
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Hercberg, Serge
(author)
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Oppert, Jean-MichelAssistance publique – Hôpitaux de Paris (AP-HP)
(author)
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Letunic, IvicaEuropean Molecular Biology Laboratory
(author)
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Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj
(author)
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Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Center for Cardiovascular and Metabolic Research (CMR),Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory(Swepub:gu)xbafre
(author)
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Ehrlich, Stanislav DuskoUniversité Paris-Saclay,University Paris-Saclay
(author)
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Dumas, Marc-EmmanuelImperial College of Science, Technology and Medicine
(author)
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Raes, JeroenKatholieke Universiteit Leuven
(author)
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Pedersen, O. B.Köpenhamns universitet,University of Copenhagen
(author)
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Clement, K.
(author)
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Stumvoll, M.Universität Leipzig,Leipzig University
(author)
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Bork, PeerEuropean Molecular Biology Laboratory
(author)
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European Molecular Biology LaboratoryUniversität Leipzig
(creator_code:org_t)
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In:Nature: Springer Science and Business Media LLC600:7889, s. 500-5050028-08361476-4687
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Coelho, Luis P.
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Fezeu, Leopold
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Helft, Gerard
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Isnard, Richard
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Ji, Boyang, 1983
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Kuhn, Michael
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Olsson, Lisa M., ...
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Pons, Nicolas
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Prifti, Edi
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Lejard, Véroniqu ...
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Levenez, Florenc ...
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Lucas-Martini, L ...
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Massey, Robin
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Martinez-Gili, L ...
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Medina-Stamminge ...
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Montalescot, Gil ...
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Moute, Sandrine
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Neves, Ana Luisa
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Le Pavin, Laetit ...
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Svendstrup, Math ...
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Gøtze, Jens P.
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Køber, Lars
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Vestergaard, H.
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Zucker, Jean-Dan ...
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Hercberg, Serge
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Oppert, Jean-Mic ...
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Nielsen, Jens B, ...
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Bäckhed, Fredrik ...
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Ehrlich, Stanisl ...
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Dumas, Marc-Emma ...
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Raes, Jeroen
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Clement, K.
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Bork, Peer
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