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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.
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; Wang, Dennis 2 ; Mason, Mike J 3
; Szalai, Bence 4 ; Bulusu, Krishna C 5 ; Guan, Yuanfang 6 ; Yu, Thomas 3
; Kang, Jaewoo 7
; Jeon, Minji 7 ; Wolfinger, Russ 8 ; Nguyen, Tin 9
; 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
; 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
; Guinney, Justin 3
; Dry, Jonathan R 170 ; Saez-Rodriguez, Julio 172
1 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
2 Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
3 Sage Bionetworks, Seattle, WA, USA
4 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
5 Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK
6 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA
7 Department of Computer Science and Engineering, Korea University, Seoul, Korea
8 SAS Institute, Inc, Cary, NC, USA
9 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




