Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.
Original languageEnglish (US)
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Jun 17 2019

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