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Abstract
We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS‐CoV‐2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large‐scale community effort to build an open access, interoperable and computable repository of COVID‐19 molecular mechanisms. The COVID‐19 Disease Map (C19DMap) is a graphical, interactive representation of disease‐relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph‐based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS‐CoV‐2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID‐19 or similar pandemics in the long‐term perspective.
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Details
; Niarakis, Anna 2
; Mazein, Alexander 1
; Kuperstein, Inna 3
; Phair, Robert 4
; Aurelio Orta‐Resendiz 5
; Singh, Vidisha 6
; Sara Sadat Aghamiri 7
; Acencio, Marcio Luis 1
; Glaab, Enrico 1
; Ruepp, Andreas 8
; Fobo, Gisela 8 ; Montrone, Corinna 8 ; Brauner, Barbara 8 ; Frishman, Goar 8 ; Luis Cristóbal Monraz Gómez 3 ; Somers, Julia 9
; Hoch, Matti 10
; Gupta, Shailendra Kumar 10
; Scheel, Julia 10
; Borlinghaus, Hanna 11 ; Czauderna, Tobias 12
; Schreiber, Falk 13 ; Montagud, Arnau 14
; Ponce de Leon, Miguel 14
; Funahashi, Akira 15
; Hiki, Yusuke 15
; Hiroi, Noriko 16
; Yamada, Takahiro G 15
; Dräger, Andreas 17
; Renz, Alina 18
; Naveez, Muhammad 19
; Bocskei, Zsolt 20
; Messina, Francesco 21
; Börnigen, Daniela 22
; Fergusson, Liam 23 ; Conti, Marta 24 ; Rameil, Marius 24
; Nakonecnij, Vanessa 24 ; Vanhoefer, Jakob 24
; Schmiester, Leonard 25
; Wang, Muying 26 ; Ackerman, Emily E 26
; Shoemaker, Jason E 27
; Zucker, Jeremy 28
; Oxford, Kristie 28
; Teuton, Jeremy 28
; Kocakaya, Ebru 29
; Gökçe Yağmur Summak 29
; Hanspers, Kristina 30
; Kutmon, Martina 31
; Coort, Susan 32
; Eijssen, Lars 33
; Ehrhart, Friederike 33
; Devasahayam Arokia Balaya Rex 34
; Slenter, Denise 32
; Martens, Marvin 32
; Pham, Nhung 32
; Haw, Robin 35
; Jassal, Bijay 35
; Matthews, Lisa 36
; Marija Orlic‐Milacic 35
; Senff-Ribeiro, Andrea 37
; Rothfels, Karen 35
; Shamovsky, Veronica 36 ; Stephan, Ralf 35
; Sevilla, Cristoffer 38
; Varusai, Thawfeek 38
; Jean‐Marie Ravel 39
; Fraser, Rupsha 40
; Ortseifen, Vera 41
; Marchesi, Silvia 42
; Gawron, Piotr 43
; Smula, Ewa 1
; Heirendt, Laurent 1
; Satagopam, Venkata 1
; Wu, Guanming 44
; Riutta, Anders 30
; Golebiewski, Martin 45
; Owen, Stuart 46
; Goble, Carole 46
; Hu, Xiaoming 45
; Overall, Rupert W 47
; Maier, Dieter 48 ; Bauch, Angela 48
; Gyori, Benjamin M 49
; Bachman, John A 49
; Vega, Carlos 1
; Grouès, Valentin 1
; Vazquez, Miguel 14
; Porras, Pablo 38
; Licata, Luana 50
; Iannuccelli, Marta 50 ; Sacco, Francesca 50
; Nesterova, Anastasia 51
; Yuryev, Anton 51 ; de Waard, Anita 52
; Turei, Denes 53
; Luna, Augustin 54
; Babur, Ozgun 55
; Soliman, Sylvain 56
; Valdeolivas, Alberto 53
; Marina Esteban‐Medina 57
; Maria Peña‐Chilet 58
; Kinza Rian 57
; Helikar, Tomáš 59
; Bhanwar Lal Puniya 59
; Modos, Dezso 60
; Treveil, Agatha 60
; Marton Olbei 60
; Bertrand De Meulder 61
; Ballereau, Stephane 62
; Dugourd, Aurélien 63
; Naldi, Aurélien 56
; Noël, Vincent 3
; Calzone, Laurence 3
; Sander, Chris 54
; Demir, Emek 9
; Korcsmaros, Tamas 60
; Freeman, Tom C 64
; Augé, Franck 20
; Beckmann, Jacques S 65
; Hasenauer, Jan 66
; Wolkenhauer, Olaf 10
; Willighagen, Egon L 32
; Pico, Alexander R 30
; Evelo, Chris T 31
; Gillespie, Marc E 67
; Stein, Lincoln D 68
; Hermjakob, Henning 38
; D'Eustachio, Peter 36
; Julio Saez‐Rodriguez 53
; Dopazo, Joaquin 69
; Valencia, Alfonso 70
; Kitano, Hiroaki 71
; Barillot, Emmanuel 3
; Auffray, Charles 61
; Balling, Rudi 1
; Schneider, Reinhard 1
1 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch‐sur‐Alzette, Luxembourg
2 Université Paris‐Saclay, Laboratoire Européen de Recherche pour la Polyarthrite rhumatoïde ‐ Genhotel, Univ Evry, Evry, France; Lifeware Group, Inria Saclay‐Ile de France, Palaiseau, France
3 Institut Curie, PSL Research University, Paris, France; INSERM, Paris, France; MINES ParisTech, PSL Research University, Paris, France
4 Integrative Bioinformatics, Inc., Mountain View, CA, USA
5 Institut Pasteur, Université de Paris, Unité HIV, Inflammation et Persistance, Paris, France; Bio Sorbonne Paris Cité, Université de Paris, Paris, France
6 Université Paris‐Saclay, Laboratoire Européen de Recherche pour la Polyarthrite rhumatoïde ‐ Genhotel, Univ Evry, Evry, France
7 Inserm‐ Institut national de la santé et de la recherche médicale, Paris, France
8 Institute of Experimental Genetics (IEG), Helmholtz Zentrum München‐German Research Center for Environmental Health (GmbH), Neuherberg, Germany
9 Department of Molecular and Medical Genetics, Oregon Health & Sciences University, Portland, OR, USA
10 Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany
11 Department of Computer and Information Science, University of Konstanz, Konstanz, Germany
12 Faculty of Information Technology, Department of Human‐Centred Computing, Monash University, Clayton, Vic., Australia
13 Department of Computer and Information Science, University of Konstanz, Konstanz, Germany; Faculty of Information Technology, Department of Human‐Centred Computing, Monash University, Clayton, Vic., Australia
14 Barcelona Supercomputing Center (BSC), Barcelona, Spain
15 Department of Biosciences and Informatics, Keio University, Yokohama, Japan
16 Graduate School of Media and Governance, Keio Research Institute at SFC, Keio University, Kanagawa, Japan#
17 Computational Systems Biology of Infections and Antimicrobial‐Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, Tübingen, Germany; Department of Computer Science, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), partner site, Tübingen, Germany
18 Computational Systems Biology of Infections and Antimicrobial‐Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, Tübingen, Germany; Department of Computer Science, University of Tübingen, Tübingen, Germany
19 Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany; Institute of Applied Computer Systems, Riga Technical University, Riga, Latvia
20 Sanofi R&D, Translational Sciences, Chilly‐Mazarin, France
21 Dipartimento di Epidemiologia Ricerca Pre‐Clinica e Diagnostica Avanzata, National Institute for Infectious Diseases 'Lazzaro Spallanzani' I.R.C.C.S., Rome, Italy; COVID‐19 INMI Network Medicine for IDs Study Group, National Institute for Infectious Diseases 'Lazzaro Spallanzani' I.R.C.C.S, Rome, Italy
22 Bioinformatics Core Facility, Universitätsklinikum Hamburg‐Eppendorf, Hamburg, Germany
23 Royal (Dick) School of Veterinary Medicine, The University of Edinburgh, Edinburgh, UK
24 Faculty of Mathematics and Natural Sciences, University of Bonn, Bonn, Germany
25 Faculty of Mathematics and Natural Sciences, University of Bonn, Bonn, Germany; Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technische Universität München – German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany#
26 Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA
27 Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA
28 Pacific Northwest National Laboratory, Richland, WA, USA
29 Stem Cell Institute, Ankara University, Ankara, Turkey
30 Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA
31 Department of Bioinformatics ‐ BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands
32 Department of Bioinformatics ‐ BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands
33 Department of Bioinformatics ‐ BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands; Maastricht University Medical Centre, Maastricht, The Netherlands
34 Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
35 MaRS Centre, Ontario Institute for Cancer Research, Toronto, ON, Canada
36 NYU Grossman School of Medicine, New York, NY, USA
37 MaRS Centre, Ontario Institute for Cancer Research, Toronto, ON, Canada; Universidade Federal do Paraná, Curitiba, Brasil
38 European Bioinformatics Institute (EMBL‐EBI), European Molecular Biology Laboratory, Hinxton, Cambridgeshire, UK
39 INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, Nancy, France; Laboratoire de génétique médicale, CHRU Nancy, Nancy, France
40 Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK
41 Senior Research Group in Genome Research of Industrial Microorganisms, Center for Biotechnology, Bielefeld University, Bielefeld, Germany
42 Department of Surgical Science, Uppsala University, Uppsala, Sweden
43 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch‐sur‐Alzette, Luxembourg; Institute of Computing Science, Poznan University of Technology, Poznan, Poland
44 Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA
45 Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany
46 Department of Computer Science, The University of Manchester, Manchester, UK
47 German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany; Institute for Biology, Humboldt University of Berlin, Berlin, Germany
48 Biomax Informatics AG, Planegg, Germany
49 Harvard Medical School, Laboratory of Systems Pharmacology, Boston, MA, USA
50 Department of Biology, University of Rome Tor Vergata, Rome, Italy
51 Elsevier, Philadelphia, PA, USA
52 Research Collaborations Unit, Elsevier, Jericho, VT, USA
53 Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany
54 cBio Center, Divisions of Biostatistics and Computational Biology, Department of Data Sciences, Dana‐Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA
55 Computer Science Department, University of Massachusetts Boston, Boston, MA, USA
56 Lifeware Group, Inria Saclay‐Ile de France, Palaiseau, France
57 Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Hospital Virgen del Rocio, Sevilla, Spain; Computational Systems Medicine Group, Institute of Biomedicine of Seville (IBIS), Hospital Virgen del Rocio, Sevilla, Spain
58 Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Hospital Virgen del Rocio, Sevilla, Spain; Computational Systems Medicine Group, Institute of Biomedicine of Seville (IBIS), Hospital Virgen del Rocio, Sevilla, Spain; Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), FPS, Hospital Virgen del Rocío, Sevilla, Spain
59 Department of Biochemistry, University of Nebraska‐Lincoln, Lincoln, NE, USA
60 Quadram Institute Bioscience, Norwich, UK; Earlham Institute, Norwich, UK
61 European Institute for Systems Biology and Medicine (EISBM), Vourles, France
62 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
63 Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany; Institute of Experimental Medicine and Systems Biology, Faculty of Medicine, RWTH, Aachen University, Aachen, Germany
64 The Roslin Institute, University of Edinburgh, Edinburgh, UK
65 University of Lausanne, Lausanne, Switzerland
66 Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany; Interdisciplinary Research Unit Mathematics and Life Sciences, University of Bonn, Bonn, Germany
67 MaRS Centre, Ontario Institute for Cancer Research, Toronto, ON, Canada; St. John’s University College of Pharmacy and Health Sciences, Queens, NY, USA
68 MaRS Centre, Ontario Institute for Cancer Research, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
69 Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Hospital Virgen del Rocio, Sevilla, Spain; Computational Systems Medicine Group, Institute of Biomedicine of Seville (IBIS), Hospital Virgen del Rocio, Sevilla, Spain; Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), FPS, Hospital Virgen del Rocío, Sevilla, Spain; FPS/ELIXIR‐es, Hospital Virgen del Rocío, Sevilla, Spain
70 Barcelona Supercomputing Center (BSC), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
71 Systems Biology Institute, Tokyo, Japan; Okinawa Institute of Science and Technology Graduate School, Okinawa, Japan




