11 results on '"Spitzmueller, Andreas"'
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2. Abstract PD6-01: Novel approach to HER2 quantification: Digital pathology coupled with AI-based image and data analysis delivers objective and quantitative HER2 expression analysis for enrichment of responders to trastuzumab deruxtecan (T-DXd; DS-8201), specifically in HER2-low patients
- Author
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Gustavson, Mark, primary, Haneder, Susanne, additional, Spitzmueller, Andreas, additional, Kapil, Ansh, additional, Schneider, Katrin, additional, Cecchi, Fabiola, additional, Sridhar, Sriram, additional, Schmidt, Guenter, additional, Lakis, Sotirios, additional, Teichert, Regina, additional, Shumilov, Anatoliy, additional, Hidalgo-Sastre, Ana, additional, Wienken, Magdalena, additional, Sade, Hadassah, additional, Barrett, J. Carl, additional, and Carroll, Danielle, additional
- Published
- 2021
- Full Text
- View/download PDF
3. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
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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
4. Abstract 2795: Dissemination score of CD8+ TILs by automated image analysis is a potential marker of immune activity in human cancers
- Author
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Bentink, Stefan, primary, Spitzmueller, Andreas, additional, Tan, Tze Heng, additional, Sade, Hadassah, additional, Wu, Song, additional, Higgs, Brandon W., additional, and Steele, Keith E., additional
- Published
- 2019
- Full Text
- View/download PDF
5. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- Author
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Computer Science, 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, Computer Science, 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, and Zucknick, Manuela
- 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.
- Published
- 2019
6. Mutually exclusive expression of CD73 and PDL1 in tumors from patients (pt) with NSCLC, gastroesophageal (GE) and urothelial bladder carcinoma (UBC).
- Author
-
Martin, Philip, primary, Spitzmueller, Andreas, additional, Wu, Song, additional, Widmaier, Moritz, additional, KORN, RENE, additional, Althammer, Sonja, additional, Zha, Jiping, additional, Higgs, Brandon W., additional, Cooper, Zachary, additional, and Steele, Keith, additional
- Published
- 2017
- Full Text
- View/download PDF
7. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
-
Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2016
- Full Text
- View/download PDF
8. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
-
Biochemistry, Center for Drug Discovery, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Biochemistry, Center for Drug Discovery, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2016
9. 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., Veroli, Giovanni Y. Di, 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, Cock, Martine De, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzö, Miklós, Cubuk, Cankut, Curtis, Christina, Daele, Dries Van, 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, Maeyer, Dries De, 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, Moerbeke, Marijke Van, 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, Niz, Carlos De, 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, Troyer, Ewoud De, 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
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49/98 ,45 ,49/23 ,article ,49/39 ,631/553 ,631/114/1305 ,631/114/2415 ,631/154/1435/2163 ,692/4028/67 ,13 ,3. Good health ,49 - 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.
10. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
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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
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3. Good health - Abstract
Nat Commun 10(1), 2674 (2019). doi:10.1038/s41467-019-09799-2
11. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
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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. 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[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.
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- 2019
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