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.

Details

Title
COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms
Author
Ostaszewski, Marek 1   VIAFID ORCID Logo  ; Niarakis, Anna 2   VIAFID ORCID Logo  ; Mazein, Alexander 1   VIAFID ORCID Logo  ; Kuperstein, Inna 3   VIAFID ORCID Logo  ; Phair, Robert 4   VIAFID ORCID Logo  ; Aurelio Orta‐Resendiz 5   VIAFID ORCID Logo  ; Singh, Vidisha 6   VIAFID ORCID Logo  ; Sara Sadat Aghamiri 7   VIAFID ORCID Logo  ; Acencio, Marcio Luis 1   VIAFID ORCID Logo  ; Glaab, Enrico 1   VIAFID ORCID Logo  ; Ruepp, Andreas 8   VIAFID ORCID Logo  ; Fobo, Gisela 8 ; Montrone, Corinna 8 ; Brauner, Barbara 8 ; Frishman, Goar 8 ; Luis Cristóbal Monraz Gómez 3 ; Somers, Julia 9   VIAFID ORCID Logo  ; Hoch, Matti 10   VIAFID ORCID Logo  ; Gupta, Shailendra Kumar 10   VIAFID ORCID Logo  ; Scheel, Julia 10   VIAFID ORCID Logo  ; Borlinghaus, Hanna 11 ; Czauderna, Tobias 12   VIAFID ORCID Logo  ; Schreiber, Falk 13 ; Montagud, Arnau 14   VIAFID ORCID Logo  ; Ponce de Leon, Miguel 14   VIAFID ORCID Logo  ; Funahashi, Akira 15   VIAFID ORCID Logo  ; Hiki, Yusuke 15   VIAFID ORCID Logo  ; Hiroi, Noriko 16   VIAFID ORCID Logo  ; Yamada, Takahiro G 15   VIAFID ORCID Logo  ; Dräger, Andreas 17   VIAFID ORCID Logo  ; Renz, Alina 18   VIAFID ORCID Logo  ; Naveez, Muhammad 19   VIAFID ORCID Logo  ; Bocskei, Zsolt 20   VIAFID ORCID Logo  ; Messina, Francesco 21   VIAFID ORCID Logo  ; Börnigen, Daniela 22   VIAFID ORCID Logo  ; Fergusson, Liam 23 ; Conti, Marta 24 ; Rameil, Marius 24   VIAFID ORCID Logo  ; Nakonecnij, Vanessa 24 ; Vanhoefer, Jakob 24   VIAFID ORCID Logo  ; Schmiester, Leonard 25   VIAFID ORCID Logo  ; Wang, Muying 26 ; Ackerman, Emily E 26   VIAFID ORCID Logo  ; Shoemaker, Jason E 27   VIAFID ORCID Logo  ; Zucker, Jeremy 28   VIAFID ORCID Logo  ; Oxford, Kristie 28   VIAFID ORCID Logo  ; Teuton, Jeremy 28   VIAFID ORCID Logo  ; Kocakaya, Ebru 29   VIAFID ORCID Logo  ; Gökçe Yağmur Summak 29   VIAFID ORCID Logo  ; Hanspers, Kristina 30   VIAFID ORCID Logo  ; Kutmon, Martina 31   VIAFID ORCID Logo  ; Coort, Susan 32   VIAFID ORCID Logo  ; Eijssen, Lars 33   VIAFID ORCID Logo  ; Ehrhart, Friederike 33   VIAFID ORCID Logo  ; Devasahayam Arokia Balaya Rex 34   VIAFID ORCID Logo  ; Slenter, Denise 32   VIAFID ORCID Logo  ; Martens, Marvin 32   VIAFID ORCID Logo  ; Pham, Nhung 32   VIAFID ORCID Logo  ; Haw, Robin 35   VIAFID ORCID Logo  ; Jassal, Bijay 35   VIAFID ORCID Logo  ; Matthews, Lisa 36   VIAFID ORCID Logo  ; Marija Orlic‐Milacic 35   VIAFID ORCID Logo  ; Senff-Ribeiro, Andrea 37   VIAFID ORCID Logo  ; Rothfels, Karen 35   VIAFID ORCID Logo  ; Shamovsky, Veronica 36 ; Stephan, Ralf 35   VIAFID ORCID Logo  ; Sevilla, Cristoffer 38   VIAFID ORCID Logo  ; Varusai, Thawfeek 38   VIAFID ORCID Logo  ; Jean‐Marie Ravel 39   VIAFID ORCID Logo  ; Fraser, Rupsha 40   VIAFID ORCID Logo  ; Ortseifen, Vera 41   VIAFID ORCID Logo  ; Marchesi, Silvia 42   VIAFID ORCID Logo  ; Gawron, Piotr 43   VIAFID ORCID Logo  ; Smula, Ewa 1   VIAFID ORCID Logo  ; Heirendt, Laurent 1   VIAFID ORCID Logo  ; Satagopam, Venkata 1   VIAFID ORCID Logo  ; Wu, Guanming 44   VIAFID ORCID Logo  ; Riutta, Anders 30   VIAFID ORCID Logo  ; Golebiewski, Martin 45   VIAFID ORCID Logo  ; Owen, Stuart 46   VIAFID ORCID Logo  ; Goble, Carole 46   VIAFID ORCID Logo  ; Hu, Xiaoming 45   VIAFID ORCID Logo  ; Overall, Rupert W 47   VIAFID ORCID Logo  ; Maier, Dieter 48 ; Bauch, Angela 48   VIAFID ORCID Logo  ; Gyori, Benjamin M 49   VIAFID ORCID Logo  ; Bachman, John A 49   VIAFID ORCID Logo  ; Vega, Carlos 1   VIAFID ORCID Logo  ; Grouès, Valentin 1   VIAFID ORCID Logo  ; Vazquez, Miguel 14   VIAFID ORCID Logo  ; Porras, Pablo 38   VIAFID ORCID Logo  ; Licata, Luana 50   VIAFID ORCID Logo  ; Iannuccelli, Marta 50 ; Sacco, Francesca 50   VIAFID ORCID Logo  ; Nesterova, Anastasia 51   VIAFID ORCID Logo  ; Yuryev, Anton 51 ; de Waard, Anita 52   VIAFID ORCID Logo  ; Turei, Denes 53   VIAFID ORCID Logo  ; Luna, Augustin 54   VIAFID ORCID Logo  ; Babur, Ozgun 55   VIAFID ORCID Logo  ; Soliman, Sylvain 56   VIAFID ORCID Logo  ; Valdeolivas, Alberto 53   VIAFID ORCID Logo  ; Marina Esteban‐Medina 57   VIAFID ORCID Logo  ; Maria Peña‐Chilet 58   VIAFID ORCID Logo  ; Kinza Rian 57   VIAFID ORCID Logo  ; Helikar, Tomáš 59   VIAFID ORCID Logo  ; Bhanwar Lal Puniya 59   VIAFID ORCID Logo  ; Modos, Dezso 60   VIAFID ORCID Logo  ; Treveil, Agatha 60   VIAFID ORCID Logo  ; Marton Olbei 60   VIAFID ORCID Logo  ; Bertrand De Meulder 61   VIAFID ORCID Logo  ; Ballereau, Stephane 62   VIAFID ORCID Logo  ; Dugourd, Aurélien 63   VIAFID ORCID Logo  ; Naldi, Aurélien 56   VIAFID ORCID Logo  ; Noël, Vincent 3   VIAFID ORCID Logo  ; Calzone, Laurence 3   VIAFID ORCID Logo  ; Sander, Chris 54   VIAFID ORCID Logo  ; Demir, Emek 9   VIAFID ORCID Logo  ; Korcsmaros, Tamas 60   VIAFID ORCID Logo  ; Freeman, Tom C 64   VIAFID ORCID Logo  ; Augé, Franck 20   VIAFID ORCID Logo  ; Beckmann, Jacques S 65   VIAFID ORCID Logo  ; Hasenauer, Jan 66   VIAFID ORCID Logo  ; Wolkenhauer, Olaf 10   VIAFID ORCID Logo  ; Willighagen, Egon L 32   VIAFID ORCID Logo  ; Pico, Alexander R 30   VIAFID ORCID Logo  ; Evelo, Chris T 31   VIAFID ORCID Logo  ; Gillespie, Marc E 67   VIAFID ORCID Logo  ; Stein, Lincoln D 68   VIAFID ORCID Logo  ; Hermjakob, Henning 38   VIAFID ORCID Logo  ; D'Eustachio, Peter 36   VIAFID ORCID Logo  ; Julio Saez‐Rodriguez 53   VIAFID ORCID Logo  ; Dopazo, Joaquin 69   VIAFID ORCID Logo  ; Valencia, Alfonso 70   VIAFID ORCID Logo  ; Kitano, Hiroaki 71   VIAFID ORCID Logo  ; Barillot, Emmanuel 3   VIAFID ORCID Logo  ; Auffray, Charles 61   VIAFID ORCID Logo  ; Balling, Rudi 1   VIAFID ORCID Logo  ; Schneider, Reinhard 1   VIAFID ORCID Logo 

 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch‐sur‐Alzette, Luxembourg 
 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 
 Institut Curie, PSL Research University, Paris, France; INSERM, Paris, France; MINES ParisTech, PSL Research University, Paris, France 
 Integrative Bioinformatics, Inc., Mountain View, CA, USA 
 Institut Pasteur, Université de Paris, Unité HIV, Inflammation et Persistance, Paris, France; Bio Sorbonne Paris Cité, Université de Paris, Paris, France 
 Université Paris‐Saclay, Laboratoire Européen de Recherche pour la Polyarthrite rhumatoïde ‐ Genhotel, Univ Evry, Evry, France 
 Inserm‐ Institut national de la santé et de la recherche médicale, Paris, France 
 Institute of Experimental Genetics (IEG), Helmholtz Zentrum München‐German Research Center for Environmental Health (GmbH), Neuherberg, Germany 
 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 
Section
Articles
Publication year
2021
Publication date
Oct 2021
Publisher
EMBO Press
e-ISSN
17444292
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2586272013
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.