Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
Authors: Menden Michael P. , Wang Dennis , Mason Mike J. , Szalai Bence , Bulusu Krishna C. , Guan Yuanfang , Yu Thomas , Kang Jaewoo , Jeon Minji , Wolfinger Russ , Nguyen Tin , Zaslavskiy Mikhail ,   AstraZeneca-Sanger Drug Combination DREAM Consortium, Abante Jordi , Abecassis Barbara Schmitz , Aben Nanne , Aghamirzaie Delasa , Aittokallio Tero , Akhtari Farida S. , Al-lazikani Bissan , Alam Tanvir , Allam Amin , Allen Chad , de Almeida Mariana Pelicano , Altarawy Doaa , Alves Vinicius , Amadoz Alicia , Anchang Benedict , Antolin Albert A. , Ash Jeremy R. , Aznar Victoria Romeo , Ba-alawi Wail , Bagheri Moeen , Bajic Vladimir , Ball Gordon , Ballester Pedro J. , Baptista Delora , Bare Christopher , Bateson Mathilde , Bender Andreas , Bertrand Denis , Wijayawardena Bhagya , Boroevich Keith A. , Bosdriesz Evert , Bougouffa Salim , Bounova Gergana , Brouwer Thomas , Bryant Barbara , Calaza Manuel , Calderone Alberto , Calza Stefano , Capuzzi Stephen , Carbonell-Caballero Jose , Carlin Daniel , Carter Hannah , Castagnoli Luisa , Celebi Remzi , Cesareni Gianni , Chang Hyeokyoon , Chen Guocai , Chen Haoran , Chen Huiyuan , Cheng Lijun , Chernomoretz Ariel , Chicco Davide , Cho Kwang-Hyun , Cho Sunghwan , Choi Daeseon , Choi Jaejoon , Choi Kwanghun , Choi Minsoo , Cock Martine De , Coker Elizabeth , Cortes-Ciriano Isidro , Cserzö Miklós , Cubuk Cankut , Curtis Christina , Daele Dries Van , Dang Cuong C. , Dijkstra Tjeerd , Dopazo Joaquin , Draghici Sorin , Drosou Anastasios , Dumontier Michel , Ehrhart Friederike , Eid Fatma-Elzahraa , ElHefnawi Mahmoud , Elmarakeby Haitham , van Engelen Bo , Engin Hatice Billur , de Esch Iwan , Evelo Chris , Falcao Andre O. , Farag Sherif , Fernandez-Lozano Carlos , Fisch Kathleen , Flobak Asmund , Fornari Chiara , Foroushani Amir B. K. , Fotso Donatien Chedom , Fourches Denis , Friend Stephen , Frigessi Arnoldo , Gao Feng , Gao Xiaoting , Gerold Jeffrey M. , Gestraud Pierre , Ghosh Samik , Gillberg Jussi , Godoy-Lorite Antonia , Godynyuk Lizzy , Godzik Adam , Goldenberg Anna , Gomez-Cabrero David , Gonen Mehmet , de Graaf Chris , Gray Harry , Grechkin Maxim , Guimera Roger , Guney Emre , Haibe-Kains Benjamin , Han Younghyun , Hase Takeshi , He Di , He Liye , Heath Lenwood S. , Hellton Kristoffer H. , Helmer-Citterich Manuela , Hidalgo Marta R. , Hidru Daniel , Hill Steven M. , Hochreiter Sepp , Hong Seungpyo , Hovig Eivind , Hsueh Ya-Chih , Hu Zhiyuan , Huang Justin K , Huang R. Stephanie , Hunyady László , Hwang Jinseub , Hwang Tae Hyun , Hwang Woochang , Hwang Yongdeuk , Isayev Olexandr , Don’t Walk Oliver Bear , Jack John , Jahandideh Samad , Ji Jiadong , Jo Yousang , Kamola Piotr J. , Kanev Georgi K. , Karacosta Loukia , Karimi Mostafa , Kaski Samuel , Kazanov Marat , Khamis Abdullah M , Khan Suleiman Ali , Kiani Narsis A. , Kim Allen , Kim Jinhan , Kim Juntae , Kim Kiseong , Kim Kyung , Kim Sunkyu , Kim Yongsoo , Kim Yunseong , Kirk Paul D. W. , Kitano Hiroaki , Klambauer Gunter , Knowles David , Ko Melissa , Kohn-Luque Alvaro , Kooistra Albert J. , Kuenemann Melaine A. , Kuiper Martin , Kurz Christoph , Kwon Mijin , van Laarhoven Twan , Laegreid Astrid , Lederer Simone , Lee Heewon , Lee Jeon , Lee Yun Woo , Lepp_aho Eemeli , Lewis Richard , Li Jing , Li Lang , Liley James , Lim Weng Khong , Lin Chieh , Liu Yiyi , Lopez Yosvany , Low Joshua , Lysenko Artem , Machado Daniel , Madhukar Neel , Maeyer Dries De , Malpartida Ana Belen , Mamitsuka Hiroshi , Marabita Francesco , Marchal Kathleen , Marttinen Pekka , Mason Daniel , Mazaheri Alireza , Mehmood Arfa , Mehreen Ali , Michaut Magali , Miller Ryan A. , Mitsopoulos Costas , Modos Dezso , Moerbeke Marijke Van , Moo Keagan , Motsinger-Reif Alison , Movva Rajiv , Muraru Sebastian , Muratov Eugene , Mushthofa Mushthofa , Nagarajan Niranjan , Nakken Sigve , Nath Aritro , Neuvial Pierre , Newton Richard , Ning Zheng , Niz Carlos De , Oliva Baldo , Olsen Catharina , Palmeri Antonio , Panesar Bhawan , Papadopoulos Stavros , Park Jaesub , Park Seonyeong , Park Sungjoon , Pawitan Yudi , Peluso Daniele , Pendyala Sriram , Peng Jian , Perfetto Livia , Pirro Stefano , Plevritis Sylvia , Politi Regina , Poon Hoifung , Porta Eduard , Prellner Isak , Preuer Kristina , Pujana Miguel Angel , Ramnarine Ricardo , Reid John E. , Reyal Fabien , Richardson Sylvia , Ricketts Camir , Rieswijk Linda , Rocha Miguel , Rodriguez-Gonzalvez Carmen , Roell Kyle , Rotroff Daniel , de Ruiter Julian R. , Rukawa Ploy , Sadacca Benjamin , Safikhani Zhaleh , Safitri Fita , Sales-Pardo Marta , Sauer Sebastian , Schlichting Moritz , Seoane Jose A. , Serra Jordi , Shang Ming-Mei , Sharma Alok , Sharma Hari , Shen Yang , Shiga Motoki , Shin Moonshik , Shkedy Ziv , Shopsowitz Kevin , Sinai Sam , Skola Dylan , Smirnov Petr , Soerensen Izel Fourie , Soerensen Peter , Song Je-Hoon , Song Sang Ok , Soufan Othman , Spitzmueller Andreas , Steipe Boris , Suphavilai Chayaporn , Tamayo Sergio Pulido , Tamborero David , Tang Jing , Tanoli Zia-ur-Rehman , Tarres-Deulofeu Marc , Tegner Jesper , Thommesen Liv , Tonekaboni Seyed Ali Madani , Tran Hong , Troyer Ewoud De , Truong Amy , Tsunoda Tatsuhiko , Turu Gábor , Tzeng Guang-Yo , Verbeke Lieven , Videla Santiago , Vis Daniel , Voronkov Andrey , Votis Konstantinos , Wang Ashley , Wang Hong-Qiang Horace , Wang Po-Wei , Wang Sheng , Wang Wei , Wang Xiaochen , Wang Xin , Wennerberg Krister , Wernisch Lorenz , Wessels Lodewyk , van Westen Gerard J. P. , Westerman Bart A. , White Simon Richard , Willighagen Egon , Wurdinger Tom , Xie Lei , Xie Shuilian , Xu Hua , Yadav Bhagwan , Yau Christopher , Yeerna Huwate , Yin Jia Wei , Yu Michael , Yu MinHwan , Yun So Jeong , Zakharov Alexey , Zamichos Alexandros , Zanin Massimiliano , Zeng Li , Zenil Hector , Zhang Frederick , Zhang Pengyue , Zhang Wei , Zhao Hongyu , Zhao Lan , Zheng Wenjin , Zoufir Azedine , Zucknick Manuela , Jang In Sock , Ghazoui Zara , Ahsen Mehmet Eren , Vogel Robert , Neto Elias Chaibub , Norman Thea , Tang Eric K. Y. , Garnett Mathew J. , Veroli Giovanni Y. Di , Fawell Stephen , Stolovitzky Gustavo , Guinney Justin , Dry Jonathan R. , Saez-Rodriguez Julio 
Published: June 2019

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.