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5 results on '"De Maeyer, Dries"'

1. Viash: from scripts to pipelines

Author

Cannoodt, Robrecht, Cannoodt, Hendrik, Van de Kerckhove, Eric, Boschmans, Andy, De Maeyer, Dries, and Verbeiren, Toni

Subjects
Software Engineering (cs.SE), FOS: Computer and information sciences, Computer Science - Software Engineering, Hardware_ARITHMETICANDLOGICSTRUCTURES
Abstract

Most bioinformatics pipelines consist of software components that are tightly coupled to the logic of the pipeline itself. This limits reusability of the individual components in the pipeline or introduces maintenance overhead when they need to be reimplemented in multiple pipelines. We introduce Viash, a tool for speeding up development of robust pipelines through "code-first" prototyping, separation of concerns and code generation of modular pipeline components. By decoupling the component functionality from the pipeline logic, component functionality becomes fully pipeline-agnostic, and conversely the resulting pipelines are agnostic towards specific component requirements. This separation of concerns improves reusability of components and facilitates multidisciplinar and pan-organisational collaborations. It has been applied in a variety of projects, from proof-of-concept pipelines to supporting an international data science competition. Viash is available as an open-source project at https://github.com/viash-io/viash and documentation is available at https://viash.io., 6 pages, 3 figures

Published
2021

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

Author

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 A., 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 T., 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, 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, and Computer Science

Subjects
health care economics and organizations
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. AstraZeneca European Union Horizon 2020 research [668858 PrECISE] Joint Research Center for Computational Biomedicine (Bayer AG) National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences Wellcome Trust [102696, 206194] We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).

Published
2019

3. Network-based omics data analysis : Netwerk gebaseerde omics data analyse

Author

De Maeyer, Dries, Marchal, Kathleen, and Vanderleyden, Jos

Abstract

The omics revolution has introduced new challenges when studying interesting phenotypes. High throughput omics technologies such as next-generation sequencing and microarray technologies generate large sets of data for a single wet-lab experiment. Interpreting the resulting data from these experiments is not trivial due to the data size and the inherent noise of the underlying technologies. In addition to this, all these data lead to an ever expanding biological knowledge which has to be taken into account when analyzing new experimental results. Biological networks provide a useful and practical approach of representing this large amount of biological knowledge. Interaction networks for example provide a blueprint of biological pathways that can be activated in an organism under specific experimental conditions. These interaction networks provide an ideal representation to interpret high-throughput omics data and in addition to this, these networks can be used by computational methods to reconstruct the molecular mechanism that drives the specific phenotype under research. An illustration of using interaction networks to analyze and visualize the results of genetic screenings was performed in a first publication in the context of this thesis. To better understand the biological pathways that drive colony morphology in Saccharomyces cerevisiae, first an interaction network for this organism was constructed from publicly available interaction data and second the results of a genetic screening were mapped onto this network. Based on this analysis the biological pathways and molecular mechanism influencing colony morphology were identified and biologically corroborated. The main part of this thesis consists of the development and application of the PheNetic framework for subnetwork inference. Subnetwork inference is the computational reconstruction of the molecular mechanism responsible for an observed phenotype from interaction networks. Using high-throughput omics data, these methods “reason” about possible explanations or molecular mechanisms of how a specific phenotype works. In a first setup, i.e. proof-of-concept, the benefits of subnetwork inference methods and specifically PheNetic were illustrated. Using multiple differential expression data sets from knock—out experiments associated with reduced acid resistance in Escherichia coli, the molecular mechanisms underlying this phenotype could be identified and validated with literature data. From the results it became clear that subnetwork inference methods outperform naïve ranking of differentially expressed genes and as such the network methods could better identify the true molecular mechanisms that drive acid resistance in E. coli. A second setup was the interpretation of differential expression data using an improved version of the PheNetic framework. This application allows for the reconstruction of on the one hand the upstream regulatory network that induces the observed pattern of differential expression and on the other hand the activated downstream protein complexes and metabolic pathways in the observed phenotype. To provide a practical subnetwork inference tool that is readily applicable to experimental differential expression data a web server was developed available at http://bioinformatics.intec.ugent.be/phenetic/. In addition, the web server provides a visualization and analysis module for the interpretation of the inferrred subnetworks. A third setup was the identification of true “driver” mutations from experimental evolution experiments. Experimental evolution experiments induce a selection on an organism to adapt to an external stress, e.g. the presence of a toxic substance, limitation of nutrients, … . This type of experiments determines the genetic base of increasing fitness in a specific environment. By combining genetic data and differential expression data between the evolved and the original parent strain the molecular mechanisms associated with the increase in fitness can be identified. By assessing connectivity of the different mutations to the molecular mechanisms activated in the evolved strain, the true “driver” mutations, i.e. mutations that induce increased fitness, can be identified. This method was successfully applied on different evolution experiments in E. coli where previously known driver mutations could be identified from other mutations. status: published

Published
2016

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

Author

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, 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., 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, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzö, Miklós, 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, 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, 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, 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, De Troyer, Ewoud, 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, and Zucknick, Manuela

Subjects
3. Good health
Abstract

Nat Commun 10(1), 2674 (2019). doi:10.1038/s41467-019-09799-2

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

Author

Menden M, Wang D, Mason M, Szalai B, Bulusu K, Guan Y, Yu T, Kang J, Jeon M, Wolfinger R, Nguyen T, Zaslavskiy M, Jang I, Ghazoui Z, Ahsen M, Vogel R, Neto E, Norman T, Tang E, Garnett M, Di Veroli G, Fawell S, Stolovitzky G, Guinney J, Dry J, Saez-Rodriguez J, Abante J, Abecassis B, Aben N, Aghamirzaie D, Aittokallio T, Akhtari F, Al-lazikani B, Alam T, Allam A, Allen C, de Almeida M, Altarawy D, Alves V, Amadoz A, Anchang B, Antolin A, Ash J, Aznar V, Ba-alawi W, Bagheri M, Bajic V, Ball G, Ballester P, Baptista D, Bare C, Bateson M, Bender A, Bertrand D, Wijayawardena B, Boroevich K, 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, Cheng L, Chernomoretz A, Chicco D, Cho K, 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 C, Dijkstra T, Dopazo J, Draghici S, Drosou A, Dumontier M, Ehrhart F, Eid F, ElHefnawi M, Elmarakeby H, van Engelen B, Engin H, de Esch I, Evelo C, Falcao A, Farag S, Fernandez-Lozano C, Fisch K, Flobak A, Fornari C, Foroushani A, Fotso D, Fourches D, Friend S, Frigessi A, Gao F, Gao X, Gerold J, 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, Hellton K, Helmer-Citterich M, Hidalgo M, Hidru D, Hill S, Hochreiter S, Hong S, Hovig E, Hsueh Y, Hu Z, Huang J, Huang R, Hunyady L, Hwang J, Hwang T, Hwang W, Hwang Y, Isayev O, Walk O, Jack J, Jahandideh S, Ji J, Jo Y, Kamola P, Kanev G, Karacosta L, Karimi M, Kaski S, Kazanov M, Khamis A, Khan S, Kiani N, Kim A, Kim J, Kim K, Kim S, Kim Y, Kirk P, Kitano H, Klambauer G, Knowles D, Ko M, Kohn-Luque A, Kooistra A, Kuenemann M, Kuiper M, Kurz C, Kwon M, van Laarhoven T, Laegreid A, Lederer S, Lee H, Lee J, Lee Y, Leppaho E, Lewis R, Li J, Li L, Liley J, Lim W, Lin C, Liu Y, Lopez Y, Low J, Lysenko A, Machado D, Madhukar N, De Maeyer D, Malpartida A, Mamitsuka H, Marabita F, Marchal K, Marttinen P, Mason D, Mazaheri A, Mehmood A, Mehreen A, Michaut M, Miller R, 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, 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, Ramnarine R, Reid J, Reyal F, Richardson S, Ricketts C, Rieswijk L, Rocha M, Rodriguez-Gonzalvez C, Roell K, Rotroff D, de Ruiter J, Rukawa P, Sadacca B, Safikhani Z, Safitri F, Sales-Pardo M, Sauer S, Schlichting M, Seoane J, Serra J, Shang M, Sharma A, Sharma H, Shen Y, Shiga M, Shin M, Shkedy Z, Shopsowitz K, Sinai S, Skola D, Smirnov P, Soerensen I, Soerensen P, Song J, Song S, Soufan O, Spitzmueller A, Steipe B, Suphavilai C, Tamayo S, Tamborero D, Tang J, Tanoli Z, Tarres-Deulofeu M, Tegner J, Thommesen L, Tonekaboni S, Tran H, De Troyer E, Truong A, Tsunoda T, Turu G, Tzeng G, Verbeke L, Videla S, Vis D, Voronkov A, Votis K, Wang A, Wang H, Wang P, Wang S, Wang W, Wang X, Wennerberg K, Wernisch L, Wessels L, van Westen G, Westerman B, White S, Willighagen E, Wurdinger T, Xie L, Xie S, Xu H, Yadav B, Yau C, Yeerna H, Yin J, Yu M, Yun S, Zakharov A, Zamichos A, Zanin M, Zeng L, Zenil H, Zhang F, Zhang P, Zhang W, Zhao H, Zhao L, Zheng W, Zoufir A, Zucknick M, AstraZeneca-Sanger Drug Combinatio, Ege Üniversitesi, Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), 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, 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, 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, College of Engineering, Department of Industrial Engineering, Institute of Data Science, RS: FSE DACS IDS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: FHML MaCSBio, Promovendi NTM, Tero Aittokallio / Principal Investigator, Bioinformatics, Institute for Molecular Medicine Finland, Hu, Z, Fotso, DC, Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, 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, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, 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, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, 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, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, 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, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden, Michael P. [0000-0003-0267-5792], Mason, Mike J. [0000-0002-5652-7739], Yu, Thomas [0000-0002-5841-0198], Kang, Jaewoo [0000-0001-6798-9106], Nguyen, Tin [0000-0001-8001-9470], Ahsen, Mehmet Eren [0000-0002-4907-0427], Stolovitzky, Gustavo [0000-0002-9618-2819], Guinney, Justin [0000-0003-1477-1888], Saez-Rodriguez, Julio [0000-0002-8552-8976], Apollo - University of Cambridge Repository, Menden, Michael P [0000-0003-0267-5792], Mason, Mike J [0000-0002-5652-7739], Pathology, CCA - Cancer biology and immunology, Medical oncology laboratory, Neurosurgery, Chemistry and Pharmaceutical Sciences, AIMMS, Medicinal chemistry, Universidade do Minho, Department of Computer Science, Professorship Marttinen P., Aalto-yliopisto, and Aalto University

Subjects
Drug Resistance, 02 engineering and technology, 13, PATHWAY, Antineoplastic Combined Chemotherapy Protocols, Molecular Targeted Therapy, Càncer, lcsh:Science, media_common, Cancer, Tumor, Settore BIO/18, Settore BIO/11, Drug combinations, High-throughput screening, Drug Synergism, purl.org/becyt/ford/1.2 [https], Genomics, Machine Learning, predictions, 3. Good health, ddc, Technologie de l'environnement, contrôle de la pollution, Benchmarking, 5.1 Pharmaceuticals, Cancer treatment, Farmacogenètica, Science & Technology - Other Topics, Development of treatments and therapeutic interventions, 0210 nano-technology, Human, Drug, media_common.quotation_subject, Science, 49/23, ADAM17 Protein, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, RESOURCE, Machine learning, Genetics, Chimie, Humans, BREAST-CANCER, CELL, 49/98, Science & Technology, Antineoplastic Combined Chemotherapy Protocol, 45, MUTATIONS, Computational Biology, Androgen receptor, Breast-cancer, Gene, Cell, Inhibition, Resistance, Pathway, Mutations, Landscape, Resource, 631/114/1305, medicine.disease, Drug synergy, 49, 030104 developmental biology, Pharmacogenetics, Mutation, Ciências Médicas::Biotecnologia Médica, lcsh:Q, 631/154/1435/2163, Biomarkers, RESISTANCE, 0301 basic medicine, ING-INF/06 - BIOINGEGNERIA ELETTRONICA E INFORMATICA, Statistical methods, Computer science, General Physics and Astronomy, Datasets as Topic, Drug resistance, purl.org/becyt/ford/1 [https], Phosphatidylinositol 3-Kinases, Biotecnologia Médica [Ciências Médicas], Neoplasms, Science and technology, Phosphoinositide-3 Kinase Inhibitors, Multidisciplinary, Biomarkers, Tumor, Cell Line, Tumor, Drug Antagonism, Drug Resistance, Neoplasm, Treatment Outcome, Pharmacogenetic, article, ANDROGEN RECEPTOR, 49/39, 631/114/2415, 021001 nanoscience & nanotechnology, 692/4028/67, Multidisciplinary Sciences, 317 Pharmacy, Patient Safety, Systems biology, 3122 Cancers, INHIBITION, Computational biology, Cell Line, medicine, LANDSCAPE, Physique, Human Genome, Data Science, General Chemistry, AstraZeneca-Sanger Drug Combination DREAM Consortium, Astronomie, GENE, Good Health and Well Being, Pharmacogenomics, Genomic, Neoplasm, 631/553, Phosphatidylinositol 3-Kinase
Abstract

PubMed: 31209238, 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. © 2019, The Author(s)., National Institute for Health Research, NIHR Wellcome Trust, WT: 102696, 206194 Magyar Tudományos Akadémia, MTA Bayer 668858 PrECISE AstraZeneca, We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194)., Competing interests: K.C.B., Z.G., G.Y.D., E.K.Y.T., S.F., and J.R.D. are AstraZeneca employees. K.C.B., Z.G., E.K.Y.T., S.F., and J.R.D. are AstraZeneca shareholders. Y.G. receives personal compensation from Eli Lilly and Company, is a shareholder of Cleerly, Inc., and Ann Arbor Algorithms, Inc. M.G. receives research funding from AstraZeneca and has performed consultancy for Sanofi. The remaining authors declare no competing interests.

Published
2019

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