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

Fecha de publicación: 17/06/2019

Autores de FISABIO

Marta R Hidalgo Garcia

Autor

Autores ajenos a FISABIO

Menden, MP
Wang, D
Mason, MJ
Szalai, B
Bulusu, KC
Guan, YF
Yu, T
Kang, J
Jeon, M
Wolfinger, R
Nguyen, T
Zaslavskiy, M
Jang, IS
Ghazoui, Z
Ahsen, ME
Vogel, R
Neto, EC
Norman, T
Tang, EKY
Garnett, MJ
Di Veroli, GY
Fawell, S
Stolovitzky, G
Guinney, J
Dry, JR
Saez-Rodriguez, J
Abante, J
Abecassis, BS
Aben, N
Aghamirzaie, D
Aittokallio, T
Akhtari, FS
Al-lazikani, B
Alam, T
Allam, A
Allen, C
de Almeida, MP
Altarawy, D
Alves, V
Amadoz, A
Anchang, B
Antolin, AA
Ash, JR
Aznar, VR
Ba-alawi, W
Bagheri, M
Bajic, V
Ball, G
Ballester, PJ
Baptista, D
Bare, C
Bateson, M
Bender, A
Bertrand, D
Wijayawardena, B
Boroevich, KA
Bosdriesz, E
Bougouffa, S
Bounova, G
Brouwer, T
Bryant, B
Calaza, M
Calderone, A
Calza, S
Capuzzi, S
Carbonell-Caballero, J
Carlin, D
Carter, H
Castagnoli, L
Celebi, R
Cesareni, G
Chang, H
Chen, GC
Chen, HR
Chen, HY
Cheng, LJ
Chernomoretz, A
Chicco, D
Cho, KH
Cho, S
Choi, D
Choi, J
Choi, K
Choi, M
De Cock, M
Coker, E
Cortes-Ciriano, I
Cserzo, M
Cubuk, C
Curtis, C
Van Daele, D
Dang, CC
Dijkstra, T
Dopazo, J
Draghici, S
Drosou, A
Dumontier, M
Ehrhart, F
Eid, FE
ElHefnawi, M
Elmarakeby, H
van Engelen, B
Engin, HB
de Esch, I
Evelo, C
Falcao, AO
Farag, S
Fernandez-Lozano, C
Fisch, K
Flobak, A
Fornari, C
Foroushani, ABK
Fotso, DC
Fourches, D
Friend, S
Frigessi, A
Gao, F
Gao, XT
Gerold, JM
Gestraud, P
Ghosh, S
Gillberg, J
Godoy-Lorite, A
Godynyuk, L
Godzik, A
Goldenberg, A
Gomez-Cabrero, D
Gonen, M
de Graaf, C
Gray, H
Grechkin, M
Guimera, R
Guney, E
Haibe-Kains, B
Han, Y
Hase, T
He, D
He, LY
Heath, LS
Hellton, KH
Helmer-Citterich, M
Hidru, D
Hill, SM
Hochreiter, S
Hong, S
Hovig, E
Hsueh, YC
Hu, ZY
Huang, JK
Huang, RS
Hunyady, L
Hwang, J
Hwang, TH
Hwang, W
Hwang, Y
Isayev, O
Walk, OBD
Jack, J
Jahandideh, S
Ji, JD
Jo, Y
Kamola, PJ
Kanev, GK
Karacosta, L
Karimi, M
Kaski, S
Kazanov, M
Khamis, AM
Khan, SA
Kiani, NA
Kim, A
Kim, J
Kim, J
Kim, K
Kim, K
Kim, S
Kim, Y
Kim, Y
Kirk, PDW
Kitano, H
Klambauer, G
Knowles, D
Ko, M
Kohn-Luque, A
Kooistra, AJ
Kuenemann, MA
Kuiper, M
Kurz, C
Kwon, M
van Laarhoven, T
Laegreid, A
Lederer, S
Lee, H
Lee, J
Lee, YW
Leppaho, E
Lewis, R
Li, J
Li, L
Liley, J
Lim, WK
Lin, C
Liu, YY
Lopez, Y
Low, J
Lysenko, A
Machado, D
Madhukar, N
De Maeyer, D
Malpartida, AB
Mamitsuka, H
Marabita, F
Marchal, K
Marttinen, P
Mason, D
Mazaheri, A
Mehmood, A
Mehreen, A
Michaut, M
Miller, RA
Mitsopoulos, C
Modos, D
Van Moerbeke, M
Moo, K
Motsinger-Reif, A
Movva, R
Muraru, S
Muratov, E
Mushthofa, M
Nagarajan, N
Nakken, S
Nath, A
Neuvial, P
Newton, R
Ning, Z
De Niz, C
Oliva, B
Olsen, C
Palmeri, A
Panesar, B
Papadopoulos, S
Park, J
Park, S
Park, S
Pawitan, Y
Peluso, D
Pendyala, S
Peng, J
Perfetto, L
Pirro, S
Plevritis, S
Politi, R
Poon, H
Porta, E
Prellner, I
Preuer, K
Pujana, MA
Ramnarine, R
Reid, JE
Reyal, F
Richardson, S
Ricketts, C
Rieswijk, L
Rocha, M
Rodriguez-Gonzalvez, C
Roell, K
Rotroff, D
de Ruiter, JR
Rukawa, P
Sadacca, B
Safikhani, Z
Safitri, F
Sales-Pardo, M
Sauer, S
Schlichting, M
Seoane, JA
Serra, J
Shang, MM
Sharma, A
Sharma, H
Shen, Y
Shiga, M
Shin, M
Shkedy, Z
Shopsowitz, K
Sinai, S
Skola, D
Smirnov, P
Soerensen, IF
Soerensen, P
Song, JH
Song, SO
Soufan, O
Spitzmueller, A
Steipe, B
Suphavilai, C
Tamayo, SP
Tamborero, D
Tang, J
Tanoli, ZUR
Tarres-Deulofeu, M
Tegner, J
Thommesen, L
Tonekaboni, SAM
Tran, H
De Troyer, E
Truong, A
Tsunoda, T
Turu, G
Tzeng, GY
Verbeke, L
Videla, S
Vis, D
Voronkov, A
Votis, K
Wang, A
Wang, HQH
Wang, PW
Wang, S
Wang, W
Wang, XC
Wang, X
Wennerberg, K
Wernisch, L
Wessels, L
van Westen, GJP
Westerman, BA
White, SR
Willighagen, E
Wurdinger, T
Xie, L
Xie, SL
Xu, H
Yadav, B
Yau, C
Yeerna, H
Yin, JW
Yu, M
Yu, M
Yun, SJ
Zakharov, A
Zamichos, A
Zanin, M
Zeng, L
Zenil, H
Zhang, F
Zhang, PY
Zhang, W
Zhao, HY
Zhao, L
Zheng, WJ
Zoufir, A
Zucknick, M
AstraZeneca-Sanger Drug Combinatio

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.