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  1. Pubblicazioni

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

Articolo
Data di Pubblicazione:
2019
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
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
ADAM17 Protein; Antineoplastic Combined Chemotherapy Protocols; Benchmarking; Biomarkers, Tumor; Cell Line, Tumor; Computational Biology; Datasets as Topic; Drug Antagonism; Drug Resistance, Neoplasm; Drug Synergism; Genomics; Humans; Molecular Targeted Therapy; Mutation; Neoplasms; Pharmacogenetics; Phosphatidylinositol 3-Kinases; Treatment Outcome
Elenco autori:
Menden, M. P.; Wang, D.; Mason, M. J.; Szalai, B.; Bulusu, K. C.; Guan, Y.; Yu, T.; Kang, J.; Jeon, M.; Wolfinger, R.; Nguyen, T.; Zaslavskiy, M.; Abante, J.; Abecassis, B. S.; Aben, N.; Aghamirzaie, D.; Aittokallio, T.; Akhtari, F. S.; Al-lazikani, B.; Alam, T.; Allam, A.; Allen, C.; de Almeida, M. P.; Altarawy, D.; Alves, V.; Amadoz, A.; Anchang, B.; Antolin, A. A.; Ash, J. R.; Aznar, V. R.; Ba-alawi, W.; Bagheri, M.; Bajic, V.; Ball, G.; Ballester, P. J.; Baptista, D.; Bare, C.; Bateson, M.; Bender, A.; Bertrand, D.; Wijayawardena, B.; Boroevich, K. A.; 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, G.; Chen, H.; Chen, H.; Cheng, L.; Chernomoretz, A.; Chicco, D.; Cho, K. -H.; Cho, S.; Choi, D.; Choi, J.; Choi, K.; Choi, M.; Cock, M. D.; Coker, E.; Cortes-Ciriano, I.; Cserzo, M.; Cubuk, C.; Curtis, C.; Daele, D. V.; Dang, C. C.; Dijkstra, T.; Dopazo, J.; Draghici, S.; Drosou, A.; Dumontier, M.; Ehrhart, F.; Eid, F. -E.; Elhefnawi, M.; Elmarakeby, H.; van Engelen, B.; Engin, H. B.; de Esch, I.; Evelo, C.; Falcao, A. O.; Farag, S.; Fernandez-Lozano, C.; Fisch, K.; Flobak, A.; Fornari, C.; Foroushani, A. B. K.; Fotso, D. C.; Fourches, D.; Friend, S.; Frigessi, A.; Gao, F.; Gao, X.; Gerold, J. M.; 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, L.; Heath, L. S.; Hellton, K. H.; Helmer-Citterich, M.; Hidalgo, M. R.; Hidru, D.; Hill, S. M.; Hochreiter, S.; Hong, S.; Hovig, E.; Hsueh, Y. -C.; Hu, Z.; Huang, J. K.; Huang, R. S.; Hunyady, L.; Hwang, J.; Hwang, T. H.; Hwang, W.; Hwang, Y.; Isayev, O.; Don't Walk, O. B.; Jack, J.; Jahandideh, S.; Ji, J.; Jo, Y.; Kamola, P. J.; Kanev, G. K.; Karacosta, L.; Karimi, M.; Kaski, S.; Kazanov, M.; Khamis, A. M.; Khan, S. A.; Kiani, N. A.; Kim, A.; Kim, J.; Kim, J.; Kim, K.; Kim, K.; Kim, S.; Kim, Y.; Kim, Y.; Kirk, P. D. W.; Kitano, H.; Klambauer, G.; Knowles, D.; Ko, M.; Kohn-Luque, A.; Kooistra, A. J.; Kuenemann, M. A.; Kuiper, M.; Kurz, C.; Kwon, M.; van Laarhoven, T.; Laegreid, A.; Lederer, S.; Lee, H.; Lee, J.; Lee, Y. W.; Lepp_aho, E.; Lewis, R.; Li, J.; Li, L.; Liley, J.; Lim, W. K.; Lin, C.; Liu, Y.; Lopez, Y.; Low, J.; Lysenko, A.; Machado, D.; Madhukar, N.; Maeyer, D. D.; Malpartida, A. B.; Mamitsuka, H.; Marabita, F.; Marchal, K.; Marttinen, P.; Mason, D.; Mazaheri, A.; Mehmood, A.; Mehreen, A.; Michaut, M.; Miller, R. A.; Mitsopoulos, C.; Modos, D.; Moerbeke, M. V.; 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.; Niz, C. D.; 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, M. A.; Ramnarine, R.; Reid, J. E.; Reyal, F.; Richardson, S.; Ricketts, C.; Rieswijk, L.; Rocha, M.; Rodriguez-Gonzalvez, C.; Roell, K.; Rotroff, D.; de Ruiter, J. R.; Rukawa, P.; Sadacca, B.; Safikhani, Z.; Safitri, F.; Sales-Pardo, M.; Sauer, S.; Schlichting, M.; Seoane, J. A.; Serra, J.; Shang, M. -M.; Sharma, A.; Sharma, H.; Shen, Y.; Shiga, M.; Shin, M.; Shkedy, Z.; Shopsowitz, K.; Sinai, S.; Skola, D.; Smirnov, P.; Soerensen, I. F.; Soerensen, P.; Song, J. -H.; Song, S. O.; Soufan, O.; Spitzmueller, A.; Steipe, B.; Suphavilai, C.; Tamayo, S. P.; Tamborero, D.; Tang, J.; Tanoli, Z. -U. -R.; Tarres-Deulofeu, M.; Tegner, J.; Thommesen, L.; Tonekaboni, S. A. M.; Tran, H.; Troyer, E. D.; Truong, A.; Tsunoda, T.; Turu, G.; Tzeng, G. -Y.; Verbeke, L.; Videla, S.; Vis, D.; Voronkov, A.; Votis, K.; Wang, A.; Wang, H. -Q. H.; Wang, P. -W.; Wang, S.; W
Autori di Ateneo:
CALZA STEFANO
Link alla scheda completa:
https://iris.unibs.it/handle/11379/524044
Link al Full Text:
https://iris.unibs.it/retrieve/handle/11379/524044/132808/491cfa9d-8b7e-0d1d-ab9d-6f0868e30e97.pdf
Pubblicato in:
NATURE COMMUNICATIONS
Journal
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