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http://hdl.handle.net/1942/29543| Title: | 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 Jang, In Sock Ghazoui, Zara Ahsen, Mehmet Eren Vogel, Robert Neto, Elias Chaibub Norman, Thea Tang, Eric K. Y. Garnett, Mathew J. Di Veroli, Giovanni Y. Fawell, Stephen Stolovitzky, Gustavo Guinney, Justin Dry, Jonathan R. Saez-Rodriguez, Julio 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. Romeo Aznar, Victoria 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 De Cock, Martine Coker, Elizabeth Cortes-Ciriano, Isidro Cserzo, Miklos Cubuk, Cankut Curtis, Christina Van Daele, Dries 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, Laszlo Hwang, Jinseub Hwang, Tae Hyun Hwang, Woochang Hwang, Yongdeuk Isayev, Olexandr Walk, Oliver Bear Don't 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 Leppaho, 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 De Maeyer, Dries 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 VAN MOERBEKE, Marijke 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 De Niz, Carlos 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 Angel Pujana, Miguel 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 DE TROYER, Ewoud Truong, Amy Tsunoda, Tatsuhiko Turu, Gabor 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, Weixin 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 |
Issue Date: | 2019 | Publisher: | NATURE PUBLISHING GROUP | Source: | NATURE COMMUNICATIONS, 10 (Art N° 2674) | 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. | Notes: | [Menden, Michael P.; Wang, Dennis; Bulusu, Krishna C.; Ghazoui, Zara; Tang, Eric K. Y.; Fornari, Chiara] AstraZeneca, IMED Biotech Unit, Oncol, Cambridge SG8 6EH, England. [Menden, Michael P.; Saez-Rodriguez, Julio] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Wang, Dennis] Univ Sheffield, Sheffield Inst Translat Neurosci, Sheffield S10 2TN, S Yorkshire, England. [Mason, Mike J.; Yu, Thomas; Jang, In Sock; Neto, Elias Chaibub; Norman, Thea; Guinney, Justin; Bare, Christopher; Friend, Stephen; Truong, Amy] Sage Bionetworks, Seattle, WA 98121 USA. 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[Zhao, Lan] City Univ Hong Kong, Dept Elect Engn, Hong Kong 999077, Peoples R China. | Keywords: | Multidisciplinary Sciences | Document URI: | http://hdl.handle.net/1942/29543 | e-ISSN: | 2041-1723 | DOI: | 10.1038/s41467-019-09799-2 | ISI #: | 000471758500010 | Rights: | The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
| Appears in Collections: | Research publications |
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|---|---|---|---|---|
| s41467-019-09799-2.pdf | Published version | 1.61 MB | Adobe PDF | View/Open |
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