Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Details

Title
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
Author
Menden, Michael P 1   VIAFID ORCID Logo  ; Wang, Dennis 2 ; Mason, Mike J 3   VIAFID ORCID Logo  ; Szalai, Bence 4 ; Bulusu, Krishna C 5 ; Guan, Yuanfang 6 ; Yu, Thomas 3   VIAFID ORCID Logo  ; Kang, Jaewoo 7   VIAFID ORCID Logo  ; Jeon, Minji 7 ; Wolfinger, Russ 8 ; Nguyen, Tin 9   VIAFID ORCID Logo  ; Zaslavskiy, Mikhail 10 ; Abante, Jordi 11 ; Schmitz Abecassis, Barbara 12 ; Aben, Nanne 13 ; Delasa Aghamirzaie 14 ; Aittokallio, Tero 15 ; Akhtari, Farida S 16 ; Al-lazikani, Bissan 17 ; Alam, Tanvir 18 ; Allam, Amin 19 ; Allen, Chad 20 ; Mariana Pelicano de Almeida 12 ; Altarawy, Doaa 21 ; Alves, Vinicius 22 ; Amadoz, Alicia 23 ; Benedict Anchang 24 ; Antolin, Albert A 17 ; Ash, Jeremy R 25 ; Victoria Romeo Aznar 26 ; Ba-alawi, Wail 18 ; Bagheri, Moeen 27 ; Bajic, Vladimir 18 ; Ball, Gordon 28 ; Ballester, Pedro J 29 ; Baptista, Delora 30 ; Bare, Christopher 3 ; Bateson, Mathilde 31 ; Bender, Andreas 20 ; Bertrand, Denis 32 ; Bhagya Wijayawardena 33 ; Boroevich, Keith A 34 ; Bosdriesz, Evert 35 ; Bougouffa, Salim 18 ; Bounova, Gergana 36 ; Brouwer, Thomas 37 ; Bryant, Barbara 38 ; Calaza, Manuel 39 ; Calderone, Alberto 40 ; Calza, Stefano 41 ; Capuzzi, Stephen 22 ; Carbonell-Caballero, Jose 42 ; Carlin, Daniel 43 ; Carter, Hannah 43 ; Castagnoli, Luisa 44 ; Celebi, Remzi 45 ; Cesareni, Gianni 44 ; Chang, Hyeokyoon 7 ; Chen, Guocai 46 ; Chen, Haoran 47 ; Chen, Huiyuan 48 ; Cheng, Lijun 33 ; Chernomoretz, Ariel 26 ; Chicco, Davide 49 ; Cho, Kwang-Hyun 50 ; Cho, Sunghwan 50 ; Choi, Daeseon 51 ; Choi, Jaejoon 52 ; Choi, Kwanghun 7 ; Choi, Minsoo 51 ; De Cock, Martine 53 ; Coker, Elizabeth 17 ; Cortes-Ciriano, Isidro 54 ; Cserzö, Miklós 55 ; Cubuk, Cankut 56 ; Curtis, Christina 57 ; Dries Van Daele 58 ; Dang, Cuong C 29 ; Dijkstra, Tjeerd 59 ; Dopazo, Joaquin 56 ; Draghici, Sorin 60 ; Drosou, Anastasios 61 ; Dumontier, Michel 62 ; Ehrhart, Friederike 12 ; Eid, Fatma-Elzahraa 63 ; ElHefnawi, Mahmoud 64 ; Elmarakeby, Haitham 63 ; Bo van Engelen 12 ; Engin, Hatice Billur 43 ; de Esch, Iwan 65 ; Evelo, Chris 12 ; Falcao, Andre O 66 ; Farag, Sherif 22 ; Fernandez-Lozano, Carlos 67 ; Fisch, Kathleen 68 ; Asmund Flobak 69 ; Fornari, Chiara 5 ; Foroushani, Amir B K 70 ; Fotso, Donatien Chedom 71 ; Fourches, Denis 72 ; Friend, Stephen 3 ; Frigessi, Arnoldo 73 ; Gao, Feng 74 ; Gao, Xiaoting 75 ; Gerold, Jeffrey M 76 ; Gestraud, Pierre 77 ; Ghosh, Samik 78 ; Gillberg, Jussi 79 ; Godoy-Lorite, Antonia 80 ; Godynyuk, Lizzy 12 ; Godzik, Adam 81 ; Goldenberg, Anna 82 ; Gomez-Cabrero, David 83 ; Gonen, Mehmet 84 ; de Graaf, Chris 65 ; Gray, Harry 85 ; Grechkin, Maxim 86 ; Guimera, Roger 87 ; Guney, Emre 88 ; Haibe-Kains, Benjamin 89 ; Han, Younghyun 50 ; Hase, Takeshi 78 ; He, Di 90 ; He, Liye 15 ; Heath, Lenwood S 91 ; Hellton, Kristoffer H 92 ; Helmer-Citterich, Manuela 44 ; Hidalgo, Marta R 56 ; Hidru, Daniel 27 ; Hill, Steven M 85 ; Hochreiter, Sepp 93 ; Hong, Seungpyo 94 ; Hovig, Eivind 95 ; Ya-Chih Hsueh 27 ; Hu, Zhiyuan 96 ; Huang, Justin K 97 ; Huang, R Stephanie 98 ; Hunyady, László 55 ; Hwang, Jinseub 99 ; Hwang, Tae Hyun 100 ; Hwang, Woochang 52 ; Hwang, Yongdeuk 101 ; Isayev, Olexandr 22 ; Oliver Bear Don’t Walk IV 102 ; Jack, John 16 ; Jahandideh, Samad 81 ; Ji, Jiadong 103 ; Yousang Jo 50 ; Kamola, Piotr J 34 ; Kanev, Georgi K 65 ; Karacosta, Loukia 24 ; Karimi, Mostafa 11 ; Kaski, Samuel 79 ; Kazanov, Marat 104 ; Khamis, Abdullah M 18 ; Suleiman Ali Khan 15 ; Kiani, Narsis A 105 ; Kim, Allen 86 ; Kim, Jinhan 106 ; Kim, Juntae 50 ; Kim, Kiseong 50 ; Kim, Kyung 107 ; Kim, Sunkyu 7 ; Kim, Yongsoo 108 ; Kim, Yunseong 50 ; Kirk, Paul D W 85 ; Kitano, Hiroaki 78 ; Klambauer, Gunter 93 ; Knowles, David 109 ; Ko, Melissa 110 ; Kohn-Luque, Alvaro 111 ; Kooistra, Albert J 65 ; Kuenemann, Melaine A 72 ; Kuiper, Martin 112 ; Kurz, Christoph 113 ; Kwon, Mijin 50 ; Twan van Laarhoven 114 ; Laegreid, Astrid 112 ; Lederer, Simone 114 ; Lee, Heewon 7 ; Jeon, Lee 100 ; Yun Woo Lee 51 ; Eemeli Lepp_aho 79 ; Lewis, Richard 20 ; Li, Jing 48 ; Lang, Li 115 ; Liley, James 116 ; Weng Khong Lim 117 ; Lin, Chieh 118 ; Liu, Yiyi 75 ; Lopez, Yosvany 119 ; Low, Joshua 12 ; Lysenko, Artem 34 ; Machado, Daniel 30 ; Neel Madhukar 120 ; Dries De Maeyer 121 ; Malpartida, Ana Belen 12 ; Mamitsuka, Hiroshi 122 ; Marabita, Francesco 28 ; Marchal, Kathleen 121 ; Marttinen, Pekka 123 ; Mason, Daniel 20 ; Mazaheri, Alireza 105 ; Mehmood, Arfa 124 ; Ali Mehreen 125 ; Michaut, Magali 36 ; Miller, Ryan A 12 ; Mitsopoulos, Costas 17 ; Modos, Dezso 20 ; Marijke Van Moerbeke 126 ; Keagan Moo 86 ; Motsinger-Reif, Alison 16 ; Movva, Rajiv 127 ; Muraru, Sebastian 12 ; Muratov, Eugene 22 ; Mushthofa, Mushthofa 128 ; Nagarajan, Niranjan 32 ; Nakken, Sigve 129 ; Nath, Aritro 98 ; Neuvial, Pierre 129 ; Newton, Richard 130 ; Zheng, Ning 131 ; De Niz, Carlos 132 ; Oliva, Baldo 133 ; Olsen, Catharina 134 ; Palmeri, Antonio 44 ; Panesar, Bhawan 27 ; Papadopoulos, Stavros 61 ; Park, Jaesub 50 ; Park, Seonyeong 51 ; Park, Sungjoon 7 ; Pawitan, Yudi 131 ; Peluso, Daniele 44 ; Pendyala, Sriram 135 ; Peng, Jian 136 ; Perfetto, Livia 44 ; Pirro, Stefano 44 ; Plevritis, Sylvia 24 ; Politi, Regina 22 ; Poon, Hoifung 137 ; Porta, Eduard 81 ; Prellner, Isak 138 ; Preuer, Kristina 93 ; Pujana, Miguel Angel 139 ; Ramnarine, Ricardo 27 ; Reid, John E 85 ; Reyal, Fabien 140 ; Richardson, Sylvia 85 ; Ricketts, Camir 120 ; Rieswijk, Linda 141 ; Rocha, Miguel 30 ; Rodriguez-Gonzalvez, Carmen 17 ; Roell, Kyle 16 ; Rotroff, Daniel 16 ; de Ruiter, Julian R 142 ; Rukawa, Ploy 130 ; Sadacca, Benjamin 140 ; Safikhani, Zhaleh 89 ; Safitri, Fita 143 ; Sales-Pardo, Marta 80 ; Sauer, Sebastian 144 ; Schlichting, Moritz 12 ; Seoane, Jose A 57 ; Serra, Jordi 139 ; Ming-Mei Shang 28 ; Sharma, Alok 145 ; Sharma, Hari 27 ; Shen, Yang 11 ; Shiga, Motoki 146 ; Shin, Moonshik 50 ; Shkedy, Ziv 147 ; Shopsowitz, Kevin 148 ; Sinai, Sam 76 ; Skola, Dylan 97 ; Smirnov, Petr 89 ; Izel Fourie Soerensen 149 ; Soerensen, Peter 149 ; Je-Hoon Song 50 ; Song, Sang Ok 106 ; Othman Soufan 36 ; Spitzmueller, Andreas 150 ; Steipe, Boris 27 ; Suphavilai, Chayaporn 151 ; Sergio Pulido Tamayo 58 ; Tamborero, David 152 ; Tang, Jing 15 ; Zia-ur-Rehman Tanoli 15 ; Tarres-Deulofeu, Marc 80 ; Tegner, Jesper 153 ; Thommesen, Liv 112 ; Seyed Ali Madani Tonekaboni 89 ; Tran, Hong 91 ; De Troyer, Ewoud 147 ; Truong, Amy 3 ; Tsunoda, Tatsuhiko 119 ; Turu, Gábor 55 ; Tzeng, Guang-Yo 27 ; Verbeke, Lieven 121 ; Videla, Santiago 26 ; Vis, Daniel 36 ; Voronkov, Andrey 129 ; Votis, Konstantinos 61 ; Wang, Ashley 27 ; Hong-Qiang, Horace Wang 154 ; Po-Wei, Wang 118 ; Wang, Sheng 136 ; Wang, Wei 74 ; Wang, Xiaochen 75 ; Wang, Xin 74 ; Wennerberg, Krister 15 ; Wernisch, Lorenz 85 ; Wessels, Lodewyk 155 ; Gerard J P van Westen 156 ; Westerman, Bart A 157 ; White, Simon Richard 85 ; Willighagen, Egon 12 ; Wurdinger, Tom 157 ; Xie, Lei 158 ; Xie, Shuilian 11 ; Xu, Hua 46 ; Yadav, Bhagwan 159 ; Yau, Christopher 160 ; Yeerna, Huwate 161 ; Jia Wei Yin 28 ; Yu, Michael 97 ; Yu, MinHwan 7 ; So Jeong Yun 106 ; Zakharov, Alexey 162 ; Zamichos, Alexandros 61 ; Zanin, Massimiliano 163 ; Zeng, Li 75 ; Zenil, Hector 164 ; Zhang, Frederick 27 ; Zhang, Pengyue 165 ; Zhang, Wei 43 ; Zhao, Hongyu 75 ; Zhao, Lan 166 ; Zheng, Wenjin 46 ; Zoufir, Azedine 20 ; Zucknick, Manuela 111 ; In Sock Jang 3 ; Ghazoui, Zara 5 ; Mehmet Eren Ahsen 167   VIAFID ORCID Logo  ; Vogel, Robert 167 ; Neto, Elias Chaibub 3 ; Norman, Thea 3 ; Tang, Eric K Y 5 ; Garnett, Mathew J 168 ; Di Veroli, Giovanni Y 169 ; Fawell, Stephen 170 ; Stolovitzky, Gustavo 171   VIAFID ORCID Logo  ; Guinney, Justin 3   VIAFID ORCID Logo  ; Dry, Jonathan R 170 ; Saez-Rodriguez, Julio 172   VIAFID ORCID Logo 

 Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK; European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK; Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Munich, Germany 
 Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK 
 Sage Bionetworks, Seattle, WA, USA 
 Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary; Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University (MTA-SE), Budapest, Hungary; RWTH Aachen University, Faculty of Medicine, Joint Research Center for Computational Biomedicine, Aachen, Germany 
 Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK 
 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA 
 Department of Computer Science and Engineering, Korea University, Seoul, Korea 
 SAS Institute, Inc, Cary, NC, USA 
 Department of Computer Science and Engineering, University of Nevada, Reno, USA 
10  Independent Consultant in Computational Biology, Owkin, Inc., New York, NY, USA 
11  Department of Electrical and Computer Engineering, Texas A&M University, College Station, USA 
12  Department of Bioinformatics - BiGCaT NUTRIM Maastricht University, Maastricht, ER, The Netherlands 
13  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands; Faculty of EEMCS, Delft University of Technology, Delft, CD, The Netherlands 
14  Genetics Bioinformatics and Computational Biology Virginia Tech, Blacksburg, VA, USA 
15  Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland 
16  Bioinformatics Research Center North Carolina State University, Raleigh, NC, USA 
17  The Institute of Cancer Research, London, UK 
18  Computational Bioscience Research Center (CBRC) KAUST, Thuwal, Saudi Arabia 
19  King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia 
20  Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK 
21  Department of Computer Science Virginia Tech, Blacksburg, VA, USA; Alexandria University, Alexandria, Egypt 
22  Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, USA 
23  Department of Bioinformatics, Igenomix SL, Valencia, Spain 
24  Department of Radiology, Stanford University, Drive, Stanford, USA 
25  Bioinformatics Research Center, Department of Chemistry, Department of Statistics, North Carolina State University, Raleigh, NC, USA 
26  Leloir Institute, Buenos Aires, Argentina 
27  University of Toronto, Toronto, Canada 
28  Unit of Computational Medicine, Department of Medicine, Solna SciLifeLab Center for Molecular Medicine Karolinska Institute, Solna, Sweden 
29  INSERM U1068, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Marseille, France; CNRS UMR7258, Marseille, France 
30  Centre Biological Engineering (CEB), University of Minho, Braga, Portugal 
31  Institut HyperCube, Paris, France 
32  Computational and Systems Biology, Genome Institute of Singapore, Singapore, Singapore 
33  Indiana University School of Medicine, Indianapolis, USA 
34  Center for Integrative Medical Sciences RIKEN Japan, Kobe, Hyogo, Japan 
35  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands; Cancer Genomics Netherlands, Utrecht, Netherlands 
36  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands 
37  Computer Laboratory, University of Cambridge, Cambridge, UK 
38  Constellation Pharmaceuticals, Cambridge, USA 
39  CIMUS University of Santiago de Compostela, La Coruña, Spain 
40  Bioinformatics and Computational Biology Unit, Department of Biology, University of Rome Tor Vergata, Rome, Italy 
41  Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden 
42  Centre de Regulacio Genomica (CRG), Barcelona Institute for Science and Technology, Barcelona, Spain 
43  Department of Medicine, University of California, San Diego, La Jolla, CA, USA 
44  Department of Biology, University of Rome Tor Vergata, Rome, Italy 
45  Department of Computer Engineering, Ege University Turkey, Metro İstasyonu, Turkey 
46  University of Texas Health Science Center, Houston, USA 
47  Texas A&M University, Station, College Station, TX, USA 
48  Case Western University, Cleveland, USA 
49  Princess Margaret Cancer Centre, Toronto, Canada 
50  Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea 
51  Department of Medical Information, Kongju Nationtional University, Gongju, South Korea 
52  Bio-Synergy Research Center, Daejeon, Republic of Korea 
53  University of Washington Tacoma, Tacoma, USA 
54  Departement de Biologie Structurale et Chimie Institut Pasteur Unite de Bioinformatique Structurale CNRS UMR, Paris, France 
55  Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary; Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University (MTA-SE), Budapest, Hungary 
56  Clinical Bioinformatic Area Fundacion Progreso y Salud CDCA Hospital Virgen del Rocio, Sevilla, Spain 
57  Stanford University, Stanford, USA 
58  KU Leuven, Leuven, Belgium 
59  Max Planck Institute for Developmental Biology, Tuebingen, Germany 
60  Department of Computer Science, Wayne State University Michigan, Detroit, USA; Department of Obstetrics and Gynecology, Wayne State University Michigan, Detroit, USA 
61  CERTH-ITI, Thessaloniki, Greece 
62  Institute of Data Science, Maastricht University, Maastricht, Netherlands 
63  Department of Computer Science Virginia Tech, Blacksburg, VA, USA; Al-Azhar University, Cairo, Egypt 
64  National Research Centre, Cairo, Egypt; Nile University, Cairo, Egypt 
65  Division of Medicinal Chemistry, AIMMS Vrije Universiteit, Amsterdam, The Netherlands 
66  LaSIGE Faculdade de Ciencias Universidade de Lisboa Portugal, Lisboa, Portugal 
67  University of A Coruna, Coruña, Spain 
68  Center for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA 
69  Norwegian University of Science and Technology, Trondheim, Norway; St. Olav’s University Hospital, Trondheim, Norway 
70  Texas State University, San Marcos Texas, San Marcos, USA 
71  University of Oxford, Oxford, UK 
72  Bioinformatics Research Center, Department of Chemistry, North Carolina State University, Raleigh, NC, USA 
73  Oslo Centre for Biostatistics and Epidemiology, University of Oslo and Oslo University Hospital Norway, Oslo, Norway 
74  Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong 
75  Yale University, New Haven, USA 
76  Program for Evolutionary Dynamics, Harvard University, Cambridge, USA 
77  Institut Curie Inserm U900, Paris, France 
78  The Systems Biology Institute Tokyo, Tokyo, Japan 
79  Department of Computer Science Aalto University, Espoo, Finland 
80  Departament d’Enginyeria, Quimica Universitat Rovira i Virgili, Tarragona, Spain 
81  Sanford Burnham Prebys Medical Discovery Institute, Jolla, USA 
82  Hospital for Sick Children, Toronto, Ontario, Canada 
83  Unit of Computational Medicine, Department of Medicine, Solna SciLifeLab Center for Molecular Medicine Karolinska Institute, Solna, Sweden; Mucosal and Salivary Biology Division King’s College London Dental Institute, London, UK 
84  College of Engineering, Koc University, Istanbul, Turkey; School of Medicine, Koc University, Istanbul, Turkey 
85  MRC Biostatistics Unit University of Cambridge, Cambridge, UK 
86  University of Washington, Seattle, WA, USA 
87  Departament d’Enginyeria, Quimica Universitat Rovira i Virgili, Tarragona, Spain; ICREA, Barcelona, Spain 
88  Joint IRB-BSC-CRG Program in Computational Biology Institute for Research in Biomedicine, Barcelona, Spain 
89  Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 
90  Ph.D. Program in Computer Science, The Graduate Center, The City University of New York, New York, USA 
91  Department of Computer Science Virginia Tech, Blacksburg, VA, USA 
92  Department of Mathematics University of Oslo, Oslo, Norway 
93  Institute of Machine Learning Johannes Kepler University Linz, Linz, Austria 
94  University of Wisconsin, Madison, USA 
95  Department of Tumor Biology Institute for Cancer Research, Oslo University Hospital Norway, Oslo, Norway; Department of Informatics University of Oslo, Oslo, Norway 
96  Wellcome Trust Centre for Human Genetics University of Oxford, Oxford, UK 
97  Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA 
98  University of Minnesota, Minneapolis, USA 
99  Department of Computer Science and Statistics, Daegu University, Daegu, South Korea 
100  Department Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA 
101  Department of Computer Science, The University of Suwon, Suwon, Republic of Korea 
102  Department of Biomedical Informatics, Columbia University in the City of New York, New York, USA 
103  School of Statistics Shandong, University of Finance and Economics, Jinan, China; Department of Computer Science, Hunter College, The City University of New York, New York, NY, USA; Department of Biostatistics, School of Public Health Shandong University China, Shandong, China 
104  Skolkovo Institute of Science and Technology, Moscow, Russia; A.A.Kharkevich Institute for Information Transmission Problems, Moscow, Russia 
105  Algorithmic Dynamics Lab Unit of Computational Medicine, Department of Medicine Solna, SciLifeLab Center for Molecular Medicine Karolinska Institute, Solna, Sweden 
106  Standigm Inc, Seoul, Korea 
107  Department of Bioengineering, University of Washington, Seattle, USA 
108  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands; Division of Oncogenomics NKI, Amsterdam, CX, The Netherlands 
109  Department of Radiology, Stanford University, Drive, Stanford, USA; Department of Genetics, Stanford University, Stanford, USA 
110  Department of Cancer Biology, Stanford University Stanford, Stanford, USA 
111  Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Oslo, Norway 
112  Norwegian University of Science and Technology, Trondheim, Norway 
113  Helmholtz Zentrum Munchen Institute of Health Economics and Health Care Management, Neuherberg, Germany 
114  Data Science Radboud University, Nijmegen, Netherlands 
115  The Ohio State University College of Medicine, Department of Biomedical Informatics, Columbus, USA 
116  Department of Medicine, University of Cambridge, Cambridge, UK 
117  Centre for Computational Biology Duke-NUS, Medical School Singapore, Singapore, Singapore; SingHealth Duke-NUS Institute of Precision Medicine Singapore, Singapore, Singapore 
118  Carnegie Mellon University, Pittsburgh, USA 
119  Center for Integrative Medical Sciences RIKEN Japan, Kobe, Hyogo, Japan; Department of Medical Science, Mathematics Medical Research Institute Tokyo Medical and Dental University, Tokyo, Japan; CREST JST, Tokyo, Japan 
120  Weill Cornell Medicine, New York, NY, USA 
121  Ghent University, Gent, Belgium 
122  Bioinformatics Center Institute for Chemical Research Kyoto University, Kyoto, Japan 
123  Helsinki Institute for Information Technology HIIT, Department of Computer Science, Aalto University Finland, Espoo, Finland 
124  University of Turku, Turku, Finland 
125  Helsinki University, Helsinki, Finland 
126  Interuniversity Institute of Bioinformatics in Brussels, Ixelles, Belgium 
127  Department of Genetics, Stanford University, Stanford, USA 
128  Ghent University Bogor Agricultural University, Gent, Belgium 
129  Institut de Mathematiques de Toulouse, Universite Paul Sabatier, Toulouse, France 
130  University of Cambridge, Cambridge, UK 
131  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden 
132  Texas Tech University, Lubbock, USA 
133  Structural Bioinformatics Group GRIB IMIM, Department of Experimental and Life Sciences, Universitat Pompeu Fabra Barcelona, Catalonia, Spain 
134  Interuniversity Institute of Bioinformatics in Brussels, Ixelles, Belgium; Machine Learning Group (MLG), Department d’Informatique, Universite libre de Bruxelles (ULB), Brussels, Belgium 
135  Harvard University, Cambridge, USA 
136  University of Illinois at Urbana-Champaign Urbana, Champaign, USA 
137  Microsoft Research Redmond, Redmond, USA 
138  Cambridge Rindge and Latin High School, Cambridge, USA 
139  Catalan Institute of Oncology (ICO), Barcelona, Spain; Bellvitge Biomedical Biomedical Research Institute (IDIBELL), Barcelona, Spain 
140  Institut Curie RT2 Lab, Paris, France 
141  Department of Bioinformatics - BiGCaT NUTRIM Maastricht University, Maastricht, ER, The Netherlands; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA 
142  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands; Division of Molecular Pathology NKI, Amsterdam, CX, The Netherlands 
143  Kyungpook National University, Daegu, South Korea 
144  FOM University of Applied Sciences, Essen, Germany 
145  Center for Integrative Medical Sciences RIKEN Japan, Kobe, Hyogo, Japan; Institute for Integrated and Intelligent Systems Griffith University, Mount Gravatt, QLD, Australia; University of the South Pacific Fiji, Suva, Fiji 
146  Department of Electrical Electronic and Computer Engineering, Gifu University, Gifu, Japan 
147  Center for Statistics, Hasselt University Belgium, Hasselt, Belgium 
148  Faculty of Medicine, University of British Columbia, Kelowna, Canada 
149  Center for Quantitative Genetics and Genomics, Department of Biology and Genetics, Aarhus University, Aarhus, Denmark 
150  Technische Universitat Munchen, München, Germany 
151  Computational and Systems Biology, Genome Institute of Singapore, Singapore, Singapore; Department of Computer Science, National University of Singapore, Singapore, Singapore 
152  Research Unit on Biomedical Informatics, University Pompeu Fabra UPF, Barcelona, Spain 
153  Unit of Computational Medicine, Department of Medicine, Solna SciLifeLab Center for Molecular Medicine Karolinska Institute, Solna, Sweden; Biological and Environmental Science and Engineering, Division KAUST, Thuwal, Saudi Arabia 
154  Cancer Hospital of Chinese Academy of Sciences, Hefei, China 
155  Division of Molecular Carcinogenesis NKI, Amsterdam, CX, The Netherlands; Faculty of EEMCS, Delft University of Technology, Delft, CD, The Netherlands; Cancer Genomics Netherlands, Utrecht, Netherlands 
156  Drug Discovery and Safety Leiden, Academic Centre for Drug Research, Leiden University, Leiden, CC, The Netherlands 
157  Department of Neurosurgery, Cancer Center, Amsterdam, WX, The Netherlands 
158  Department of Computer Science, Hunter College and The Graduate Center, The City University of New York, New York, NY, USA 
159  Hematology Research Unit Helsinki, Department of Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland 
160  Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK 
161  University of California, San Diego, SD, USA 
162  National Center for Advancing Translational Sciences National Institutes of Health, Rockville, MD, USA 
163  Universidad Politecnica de Madrid, Madrid, Spain 
164  Algorithmic Dynamics Lab Unit of Computational Medicine, Department of Medicine Solna, SciLifeLab Center for Molecular Medicine Karolinska Institute, Solna, Sweden; Oxford Immune Algorithmics Ltd, Oxford, UK 
165  Indiana University - Purdue University, Indianapolis, USA 
166  Department of Electronic Engineering, City University of Hong Kong, Hong Kong, Hong Kong 
167  IBM Thomas J. Watson Research Center, Yorktown Heights, New York, USA 
168  Wellcome Trust Sanger Institute, Hinxton, UK 
169  Early Clinical Development, IMED Biotech Unit, AstraZeneca, Cambridge, UK 
170  Oncology, IMED Biotech Unit, AstraZeneca, R&D Boston, Waltham, MA, USA 
171  IBM Thomas J. Watson Research Center, Yorktown Heights, New York, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA 
172  European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK; RWTH Aachen University, Faculty of Medicine, Joint Research Center for Computational Biomedicine, Aachen, Germany; Heidelberg University, Faculty of Medicine, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany 
Pages
1-17
Publication year
2019
Publication date
Jun 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2242641659
Copyright
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