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AI is a viable alternative to high throughput screening: a 318-target study
Wallach, Izhar; Bernard, Denzil; Nguyen, Kong; Ho, Gregory; Morrison, Adrian; Stecula, Adrian; Rosnik, Andreana; O"™Sullivan, Ann Marie; Davtyan, Aram; Samudio, Ben; Thomas, Bill; Worley, Brad; Butler, Brittany; Laggner, Christian; Thayer, Desiree; Moharreri, Ehsan; Friedland, Greg; Truong, Ha; van den Bedem, Henry; Ng, Ho Leung; Stafford, Kate; Sarangapani, Krishna; Giesler, Kyle; Ngo, Lien; Mysinger, Michael; Ahmed, Mostafa; Anthis, Nicholas J.; Henriksen, Niel; Gniewek, Pawel; Eckert, Sam; de Oliveira, Saulo; Suterwala, Shabbir; PrasadPrasad, Srimukh Veccham Krishna; Shek, Stefani; Contreras, Stephanie; Hare, Stephanie; Palazzo, Teresa; O"™Brien, Terrence E.; Van Grack, Tessa; Williams, Tiffany; Chern, Ting Rong; Kenyon, Victor; Lee, Andreia H.; Cann, Andrew B.; Bergman, Bastiaan; Anderson, Brandon M.; Cox, Bryan D.; Warrington, Jeffrey M.; Sorenson, Jon M.; Goldenberg, Joshua M.; Young, Matthew A.; DeHaan, Nicholas; Pemberton, Ryan P.; Schroedl, Stefan; Abramyan, Tigran M.; Gupta, Tushita; Mysore, Venkatesh; Presser, Adam G.; Ferrando, Adolfo A.; Andricopulo, Adriano D.; Ghosh, Agnidipta; Ayachi, Aicha Gharbi; Mushtaq, Aisha; Shaqra, Ala M.; Toh, Alan Kie Leong; Smrcka, Alan V.; Ciccia, Alberto; de Oliveira, Aldo Sena; Sverzhinsky, Aleksandr; de Sousa, Alessandra Mara; Agoulnik, Alexander I.; Kushnir, Alexander; Freiberg, Alexander N.; Statsyuk, Alexander V.; Gingras, Alexandre R.; Degterev, Alexei; Tomilov, Alexey; Vrielink, Alice; Garaeva, Alisa A.; Bryant-Friedrich, Amanda; Caflisch, Amedeo; Patel, Amit K.; Rangarajan, Amith Vikram; Matheeussen, An; Battistoni, Andrea; Caporali, Andrea; Chini, Andrea; Ilari, Andrea; Mattevi, Andrea; Foote, Andrea Talbot; Trabocchi, Andrea; Stahl, Andreas; Herr, Andrew B.; Berti, Andrew; Freywald, Andrew; Reidenbach, Andrew G.; Lam, Andrew; Cuddihy, Andrew R.; White, Andrew; Taglialatela, Angelo; Ojha, Anil K.; Cathcart, Ann M.; Motyl, Anna A.L.; Borowska, Anna; D"™Antuono, Anna; Hirsch, Anna K.H.; Porcelli, Anna Maria; Minakova, Anna; Montanaro, Anna; Müller, Anna; Fiorillo, Annarita; Virtanen, Anniina; O"™Donoghue, Anthony J.; Del Rio Flores, Antonio; Garmendia, Antonio E.; Pineda-Lucena, Antonio; Panganiban, Antonito T.; Samantha, Ariela; Chatterjee, Arnab K.; Haas, Arthur L.; Paparella, Ashleigh S.; John, Ashley L.St; Prince, Ashutosh; ElSheikh, Assmaa; Apfel, Athena Marie; Colomba, Audrey; O"™Dea, Austin; Diallo, Bakary N"™tji; Ribeiro, Beatriz Murta Rezende Moraes; Bailey-Elkin, Ben A.; Edelman, Benjamin L.; Liou, Benjamin; Perry, Benjamin; Chua, Benjamin Soon Kai; Kováts, Benjámin; Englinger, Bernhard; Balakrishnan, Bijina; Gong, Bin; Agianian, Bogos; Pressly, Brandon; Salas, Brenda P.Medellin; Duggan, Brendan M.; Geisbrecht, Brian V.; Dymock, Brian W.; Morten, Brianna C.; Hammock, Bruce D.; Mota, Bruno Eduardo Fernandes; Dickinson, Bryan C.; Fraser, Cameron; Lempicki, Camille; Novina, Carl D.; Torner, Carles; Ballatore, Carlo; Bon, Carlotta; Chapman, Carly J.; Partch, Carrie L.; Chaton, Catherine T.; Huang, Chang; Yang, Chao Yie; Kahler, Charlene M.; Karan, Charles; Keller, Charles; Dieck, Chelsea L.; Huimei, Chen; Liu, Chen; Peltier, Cheryl; Mantri, Chinmay Kumar; Kemet, Chinyere Maat; Müller, Christa E.; Weber, Christian; Zeina, Christina M.; Muli, Christine S.; Morisseau, Christophe; Alkan, Cigdem; Reglero, Clara; Loy, Cody A.; Wilson, Cornelia M.; Myhr, Courtney; Arrigoni, Cristina; Paulino, Cristina; Santiago, César; Luo, Dahai; Tumes, Damon J.; Keedy, Daniel A.; Lawrence, Daniel A.; Chen, Daniel; Manor, Danny; Trader, Darci J.; Hildeman, David A.; Drewry, David H.; Dowling, David J.; Hosfield, David J.; Smith, David M.; Moreira, David; Siderovski, David P.; Shum, David; Krist, David T.; Riches, David W.H.; Ferraris, Davide Maria; Anderson, Deborah H.; Coombe, Deirdre R.; Welsbie, Derek S.; Hu, Di; Ortiz, Diana; Alramadhani, Dina; Zhang, Dingqiang; Chaudhuri, Dipayan; Slotboom, Dirk J.; Ronning, Donald R.; Lee, Donghan; Dirksen, Dorian; Shoue, Douglas A.; Zochodne, Douglas William; Krishnamurthy, Durga; Duncan, Dustin; Glubb, Dylan M.; Gelardi, Edoardo Luigi Maria; Hsiao, Edward C.; Lynn, Edward G.; Silva, Elany Barbosa; Aguilera, Elena; Lenci, Elena; Abraham, Elena Theres; Lama, Eleonora; Mameli, Eleonora; Leung, Elisa; Christensen, Emily M.; Mason, Emily R.; Petretto, Enrico; Trakhtenberg, Ephraim F.; Rubin, Eric J.; Strauss, Erick; Thompson, Erik W.; Cione, Erika; Lisabeth, Erika Mathes; Fan, Erkang; Kroon, Erna Geessien; Jo, Eunji; Garcia-Cuesta, Eva M.; Glukhov, Evgenia; Gavathiotis, Evripidis; Yu, Fang; Xiang, Fei; Leng, Fenfei; Wang, Feng; Ingoglia, Filippo; van den Akker, Focco; Borriello, Francesco; Vizeacoumar, Franco J.; Luh, Frank; Buckner, Frederick S.; Vizeacoumar, Frederick S.; Bdira, Fredj Ben; Svensson, Fredrik; Rodriguez, G. Marcela; Bognár, Gabriella; Lembo, Gaia; Zhang, Gang; Dempsey, Garrett; Eitzen, Gary; Mayer, Gaétan; Greene, Geoffrey L.; Garcia, George A.; Lukacs, Gergely L.; Prikler, Gergely; Parico, Gian Carlo G.; Colotti, Gianni; De Keulenaer, Gilles; Cortopassi, Gino; Roti, Giovanni; Girolimetti, Giulia; Fiermonte, Giuseppe; Gasparre, Giuseppe; Leuzzi, Giuseppe; Dahal, Gopal; Michlewski, Gracjan; Conn, Graeme L.; Stuchbury, Grant David; Bowman, Gregory R.; Popowicz, Grzegorz Maria; Veit, Guido; de Souza, Guilherme Eduardo; Akk, Gustav; Caljon, Guy; Alvarez, Guzmán; Rucinski, Gwennan; Lee, Gyeongeun; Cildir, Gokhan; Li, Hai; Breton, Hairol E.; Jafar-Nejad, Hamed; Zhou, Han; Moore, Hannah P.; Tilford, Hannah; Yuan, Haynes; Shim, Heesung; Wulff, Heike; Hoppe, Heinrich; Chaytow, Helena; Tam, Heng Keat; Van Remmen, Holly; Xu, Hongyang; Debonsi, Hosana Maria; Lieberman, Howard B.; Jung, Hoyoung; Fan, Hua Ying; Feng, Hui; Zhou, Hui; Kim, Hyeong Jun; Greig, Iain R.; Caliandro, Ileana; Corvo, Ileana; Arozarena, Imanol; Mungrue, Imran N.; Verhamme, Ingrid M.; Qureshi, Insaf Ahmed; Lotsaris, Irina; Cakir, Isin; Perry, J. Jefferson P.; Kwiatkowski, Jacek; Boorman, Jacob; Ferreira, Jacob; Fries, Jacob; Kratz, Jadel Müller; Miner, Jaden; Siqueira-Neto, Jair L.; Granneman, James G.; Ng, James; Shorter, James; Voss, Jan Hendrik; Gebauer, Jan M.; Chuah, Janelle; Mousa, Jarrod J.; Maynes, Jason T.; Evans, Jay D.; Dickhout, Jeffrey; MacKeigan, Jeffrey P.; Jossart, Jennifer N.; Zhou, Jia; Lin, Jiabei; Xu, Jiake; Wang, Jianghai; Zhu, Jiaqi; Liao, Jiayu; Xu, Jingyi; Zhao, Jinshi; Lin, Jiusheng; Lee, Jiyoun; Reis, Joana; Stetefeld, Joerg; Bruning, John B.; , ; Coles, John G.; Tanner, John J.; Pascal, John M.; So, Jonathan; Pederick, Jordan L.; Costoya, Jose A.; Rayman, Joseph B.; Maciag, Joseph J.; Nasburg, Joshua Alexander; Gruber, Joshua J.; Finkelstein, Joshua M.; Watkins, Joshua; Rodriguez-Frade, José Miguel; Arias, Juan Antonio Sanchez; Lasarte, Juan José; Oyarzabal, Julen; Milosavljevic, Julian; Cools, Julie; Lescar, Julien; Bogomolovas, Julijus; Wang, Jun; Kee, Jung Min; Kee, Jung Min; Liao, Junzhuo; Sistla, Jyothi C.; Abrahão, Jônatas Santos; Sishtla, Kamakshi; Francisco, Karol R.; Hansen, Kasper B.; Molyneaux, Kathleen A.; Cunningham, Kathryn A.; Martin, Katie R.; Gadar, Kavita; Ojo, Kayode K.; Wong, Keith S.; Wentworth, Kelly L.; Lai, Kent; Lobb, Kevin A.; Hopkins, Kevin M.; Parang, Keykavous; Machaca, Khaled; Pham, Kien; Ghilarducci, Kim; Sugamori, Kim S.; McManus, Kirk James; Musta, Kirsikka; Faller, Kiterie M.E.; Nagamori, Kiyo; Mostert, Konrad J.; Korotkov, Konstantin V.; Liu, Koting; Smith, Kristiana S.; Sarosiek, Kristopher; Rohde, Kyle H.; Kim, Kyu Kwang; Lee, Kyung Hyeon; Pusztai, Lajos; Lehtio, Lari; Haupt, Larisa M.; Cowen, Leah E.; Byrne, Lee J.; Su, Leila; Wert-Lamas, Leon; Puchades-Carrasco, Leonor; Chen, Lifeng; Malkas, Linda H.; Zhuo, Ling; , ; Hedstrom, Lizbeth; Walensky, Loren D.; Antonelli, Lorenzo; Iommarini, Luisa; Whitesell, Luke; Randall, Lia M.; Fathallah, M. Dahmani; Nagai, Maira Harume; Kilkenny, Mairi Louise; Ben-Johny, Manu; Lussier, Marc P.; Windisch, Marc P.; Lolicato, Marco; Lolli, Marco Lucio; Vleminckx, Margot; Caroleo, Maria Cristina; Macias, Maria J.; Valli, Marilia; Barghash, Marim M.; Mellado, Mario; Tye, Mark A.; Wilson, Mark A.; Hannink, Mark; Ashton, Mark R.; Cerna, Mark Vincent C.dela; Giorgis, Marta; Safo, Martin K.; Maurice, Martin St; McDowell, Mary Ann; Pasquali, Marzia; Mehedi, Masfique; Serafim, Mateus Sá Magalhães; Soellner, Matthew B.; Alteen, Matthew G.; Champion, Matthew M.; Skorodinsky, Maxim; O"™Mara, Megan L.; Bedi, Mel; Rizzi, Menico; Levin, Michael; Mowat, Michael; Jackson, Michael R.; Paige, Mikell; Al-Yozbaki, Minnatallah; Giardini, Miriam A.; Maksimainen, Mirko M.; De Luise, Monica; Hussain, Muhammad Saddam; Christodoulides, Myron; Stec, Natalia; Zelinskaya, Natalia; Van Pelt, Natascha; Merrill, Nathan M.; Singh, Nathanael; Kootstra, Neeltje A.; Singh, Neeraj; Gandhi, Neha S.; Chan, Nei Li; Trinh, Nguyen Mai; Schneider, Nicholas O.; Matovic, Nick; Horstmann, Nicola; Longo, Nicola; Bharambe, Nikhil; Rouzbeh, Nirvan; Mahmoodi, Niusha; Gumede, Njabulo Joyfull; Anastasio, Noelle C.; Khalaf, Noureddine Ben; Rabal, Obdulia; Kandror, Olga; Escaffre, Olivier; Silvennoinen, Olli; Bishop, Ozlem Tastan; Iglesias, Pablo; Sobrado, Pablo; Chuong, Patrick; O"™Connell, Patrick; Martin-Malpartida, Pau; Mellor, Paul; Fish, Paul V.; Moreira, Paulo Otávio Lourenço; Zhou, Pei; , ; Liu, Pengda; Wu, Pengpeng; Agogo-Mawuli, Percy; Jones, Peter L.; Ngoi, Peter; Toogood, Peter; Ip, Philbert; von Hundelshausen, Philipp; Lee, Pil H.; Rowswell-Turner, Rachael B.; Balaña-Fouce, Rafael; Rocha, Rafael Eduardo Oliveira; Guido, Rafael V.C.; Ferreira, Rafaela Salgado; Agrawal, Rajendra K.; Harijan, Rajesh K.; Ramachandran, Rajesh; Verma, Rajkumar; Singh, Rakesh K.; Tiwari, Rakesh Kumar; Mazitschek, Ralph; Koppisetti, Rama K.; Dame, Remus T.; Douville, Renée N.; Austin, Richard C.; Taylor, Richard E.; Moore, Richard G.; Ebright, Richard H.; Angell, Richard M.; Yan, Riqiang; Kejriwal, Rishabh; Batey, Robert A.; Blelloch, Robert; Vandenberg, Robert J.; Hickey, Robert J.; Kelm, Robert J.; Lake, Robert J.; Bradley, Robert K.; Blumenthal, Robert M.; Solano, Roberto; Gierse, Robin Matthias; Viola, Ronald E.; McCarthy, Ronan R.; Reguera, Rosa Maria; Uribe, Ruben Vazquez; do Monte-Neto, Rubens Lima; Gorgoglione, Ruggiero; Cullinane, Ryan T.; Katyal, Sachin; Hossain, Sakib; Phadke, Sameer; Shelburne, Samuel A.; Geden, Sandra E.; Johannsen, Sandra; Wazir, Sarah; Legare, Scott; Landfear, Scott M.; Radhakrishnan, Senthil K.; Ammendola, Serena; Dzhumaev, Sergei; Seo, Seung Yong; Li, Shan; Zhou, Shan; Chu, Shaoyou; Chauhan, Shefali; Maruta, Shinsaku; Ashkar, Shireen R.; Shyng, Show Ling; Conticello, Silvestro G.; Buroni, Silvia; Garavaglia, Silvia; White, Simon J.; Zhu, Siran; Tsimbalyuk, Sofiya; Chadni, Somaia Haque; Byun, Soo Young; Park, Soonju; Xu, Sophia Q.; Banerjee, Sourav; Zahler, Stefan; Espinoza, Stefano; Gustincich, Stefano; Sainas, Stefano; Celano, Stephanie L.; Capuzzi, Stephen J.; Waggoner, Stephen N.; Poirier, Steve; Olson, Steven H.; Marx, Steven O.; Van Doren, Steven R.; Sarilla, Suryakala; Brady-Kalnay, Susann M.; Dallman, Sydney; Azeem, Syeda Maryam; Teramoto, Tadahisa; Mehlman, Tamar; Swart, Tarryn; Abaffy, Tatjana; Akopian, Tatos; Haikarainen, Teemu; Moreda, Teresa Lozano; Ikegami, Tetsuro; Teixeira, Thaiz Rodrigues; Jayasinghe, Thilina D.; Gillingwater, Thomas H.; Kampourakis, Thomas; Richardson, Timothy I.; Herdendorf, Timothy J.; Kotzé, Timothy J.; O"™Meara, Timothy R.; Corson, Timothy W.; Hermle, Tobias; Ogunwa, Tomisin Happy; Lan, Tong; Su, Tong; Banjo, Toshihiro; O"™Mara, Tracy A.; Chou, Tristan; Chou, Tsui Fen; Baumann, Ulrich; Desai, Umesh R.; Pai, Vaibhav P.; Thai, Van Chi; Tandon, Vasudha; Banerji, Versha; Robinson, Victoria L.; Gunasekharan, Vignesh; Namasivayam, Vigneshwaran; Segers, Vincent F.M.; Maranda, Vincent; Dolce, Vincenza; Maltarollo, Vinicius Gonçalves; Scoffone, Viola Camilla; Woods, Virgil A.; Ronchi, Virginia Paola; Van Hung Le, Vuong; Clayton, W. Brent; Lowther, W. Todd; Houry, Walid A.; Li, Wei; Tang, Weiping; Zhang, Wenjun; Van Voorhis, Wesley C.; Donaldson, William A.; Hahn, William C.; Kerr, William G.; Gerwick, William H.; Bradshaw, William J.; Foong, Wuen Ee; Blanchet, Xavier; Wu, Xiaoyang; Lu, Xin; Qi, Xin; Xu, Xin; Yu, Xinfang; Qin, Xingping; Wang, Xingyou; Yuan, Xinrui; Zhang, Xu; Zhang, Yan Jessie; Hu, Yanmei; Aldhamen, Yasser Ali; Chen, Yicheng; Li, Yihe; Sun, Ying; Zhu, Yini; Gupta, Yogesh K.; Pérez-Pertejo, Yolanda; Li, Yong; Tang, Young; He, Yuan; Tse-Dinh, Yuk Ching; Sidorova, Yulia A.; Yen, Yun; Li, Yunlong; Frangos, Zachary J.; Chung, Zara; Su, Zhengchen; Wang, Zhenghe; Zhang, Zhiguo; Liu, Zhongle; Inde, Zintis; Artia, Zoraima; Heifets, Abraham
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
SCOPUS:85191821387
ISSN: 2045-2322
CID: 5658952
Correction to: AI is a viable alternative to high throughput screening: a 318-target study (Scientific Reports, (2024), 14, 1, (7526), 10.1038/s41598-024-54655-z)
Giles, Ellie; Heifets, Abraham; Artia, Zoraima; Inde, Zintis; Liu, Zhongle; Zhang, Zhiguo; Wang, Zhenghe; Su, Zhengchen; Chung, Zara; Frangos, Zachary J.; Li, Yunlong; Yen, Yun; Sidorova, Yulia A.; Tse-Dinh, Yuk Ching; He, Yuan; Tang, Young; Li, Yong; Pérez-Pertejo, Yolanda; Gupta, Yogesh K.; Zhu, Yini; Sun, Ying; Li, Yihe; Chen, Yicheng; Aldhamen, Yasser Ali; Hu, Yanmei; Zhang, Yan Jessie; Zhang, Xu; Yuan, Xinrui; Wang, Xingyou; Qin, Xingping; Yu, Xinfang; Xu, Xin; Qi, Xin; Lu, Xin; Wu, Xiaoyang; Blanchet, Xavier; Foong, Wuen Ee; Bradshaw, William J.; Gerwick, William H.; Kerr, William G.; Hahn, William C.; Donaldson, William A.; Van Voorhis, Wesley C.; Zhang, Wenjun; Tang, Weiping; Li, Wei; Houry, Walid A.; Lowther, W. Todd; Clayton, W. Brent; Van Hung Le, Vuong; Ronchi, Virginia Paola; Woods, Virgil A.; Scoffone, Viola Camilla; Maltarollo, Vinicius Gonçalves; Dolce, Vincenza; Maranda, Vincent; Segers, Vincent F.M.; Namasivayam, Vigneshwaran; Gunasekharan, Vignesh; Robinson, Victoria L.; Banerji, Versha; Tandon, Vasudha; Thai, Van Chi; Pai, Vaibhav P.; Desai, Umesh R.; Baumann, Ulrich; Chou, Tsui Fen; Chou, Tristan; O"™Mara, Tracy A.; Banjo, Toshihiro; Su, Tong; Lan, Tong; Ogunwa, Tomisin Happy; Hermle, Tobias; Corson, Timothy W.; O"™Meara, Timothy R.; Kotzé, Timothy J.; Herdendorf, Timothy J.; Richardson, Timothy I.; Kampourakis, Thomas; Gillingwater, Thomas H.; Jayasinghe, Thilina D.; Teixeira, Thaiz Rodrigues; Ikegami, Tetsuro; Moreda, Teresa Lozano; Haikarainen, Teemu; Akopian, Tatos; Abaffy, Tatjana; Swart, Tarryn; Mehlman, Tamar; Teramoto, Tadahisa; Azeem, Syeda Maryam; Dallman, Sydney; Brady-Kalnay, Susann M.; Sarilla, Suryakala; Van Doren, Steven R.; Marx, Steven O.; Olson, Steven H.; Poirier, Steve; Waggoner, Stephen N.; Capuzzi, Stephen J.; Celano, Stephanie L.; Sainas, Stefano; Gustincich, Stefano; Espinoza, Stefano; Zahler, Stefan; Banerjee, Sourav; Xu, Sophia Q.; Park, Soonju; Byun, Soo Young; Chadni, Somaia Haque; Tsimbalyuk, Sofiya; Zhu, Siran; White, Simon J.; Garavaglia, Silvia; Buroni, Silvia; Conticello, Silvestro G.; Shyng, Show Ling; Ashkar, Shireen R.; Maruta, Shinsaku; Chauhan, Shefali; Chu, Shaoyou; Zhou, Shan; Li, Shan; Seo, Seung Yong; Dzhumaev, Sergei; Ammendola, Serena; Radhakrishnan, Senthil K.; Landfear, Scott M.; Legare, Scott; Wazir, Sarah; Johannsen, Sandra; Geden, Sandra E.; Shelburne, Samuel A.; Phadke, Sameer; Hossain, Sakib; Katyal, Sachin; Cullinane, Ryan T.; Gorgoglione, Ruggiero; do Monte-Neto, Rubens Lima; Uribe, Ruben Vazquez; Reguera, Rosa Maria; McCarthy, Ronan R.; Viola, Ronald E.; Gierse, Robin Matthias; Solano, Roberto; Blumenthal, Robert M.; Bradley, Robert K.; Lake, Robert J.; Kelm, Robert J.; Hickey, Robert J.; Vandenberg, Robert J.; Blelloch, Robert; Batey, Robert A.; Kejriwal, Rishabh; Yan, Riqiang; Angell, Richard M.; Ebright, Richard H.; Moore, Richard G.; Taylor, Richard E.; Austin, Richard C.; Douville, Renée N.; Dame, Remus T.; Koppisetti, Rama K.; Mazitschek, Ralph; Tiwari, Rakesh Kumar; Singh, Rakesh K.; Verma, Rajkumar; Ramachandran, Rajesh; Harijan, Rajesh K.; Agrawal, Rajendra K.; Ferreira, Rafaela Salgado; Guido, Rafael V.C.; Rocha, Rafael Eduardo Oliveira; Balaña-Fouce, Rafael; Rowswell-Turner, Rachael B.; Lee, Pil H.; von Hundelshausen, Philipp; Ip, Philbert; Toogood, Peter; Ngoi, Peter; Jones, Peter L.; Agogo-Mawuli, Percy; Wu, Pengpeng; Liu, Pengda; Zhou, Pei; Moreira, Paulo Otávio Lourenço; Fish, Paul V.; Mellor, Paul; Martin-Malpartida, Pau; O"™Connell, Patrick; Chuong, Patrick; Sobrado, Pablo; Iglesias, Pablo; Bishop, Ozlem Tastan; Silvennoinen, Olli; Escaffre, Olivier; Kandror, Olga; Rabal, Obdulia; Khalaf, Noureddine Ben; Anastasio, Noelle C.; Gumede, Njabulo Joyfull; Mahmoodi, Niusha; Rouzbeh, Nirvan; Bharambe, Nikhil; Longo, Nicola; Horstmann, Nicola; Matovic, Nick; Schneider, Nicholas O.; Trinh, Nguyen Mai; Chan, Nei Li; Gandhi, Neha S.; Singh, Neeraj; Kootstra, Neeltje A.; Singh, Nathanael; Merrill, Nathan M.; Van Pelt, Natascha; Zelinskaya, Natalia; Stec, Natalia; Christodoulides, Myron; Hussain, Muhammad Saddam; De Luise, Monica; Maksimainen, Mirko M.; Giardini, Miriam A.; Al-Yozbaki, Minnatallah; Paige, Mikell; Jackson, Michael R.; Mowat, Michael; Levin, Michael; Rizzi, Menico; Bedi, Mel; O"™Mara, Megan L.; Skorodinsky, Maxim; Champion, Matthew M.; Alteen, Matthew G.; Soellner, Matthew B.; Serafim, Mateus Sá Magalhães; Mehedi, Masfique; Pasquali, Marzia; McDowell, Mary Ann; Maurice, Martin St; Safo, Martin K.; Giorgis, Marta; Cerna, Mark Vincent C.dela; Ashton, Mark R.; Hannink, Mark; Wilson, Mark A.; Tye, Mark A.; Mellado, Mario; Barghash, Marim M.; Valli, Marilia; Macias, Maria J.; Caroleo, Maria Cristina; Vleminckx, Margot; Lolli, Marco Lucio; Lolicato, Marco; Windisch, Marc P.; Lussier, Marc P.; Ben-Johny, Manu; Kilkenny, Mairi Louise; Nagai, Maira Harume; Fathallah, M. Dahmani; Randall, Lia M.; Whitesell, Luke; Iommarini, Luisa; Antonelli, Lorenzo; Walensky, Loren D.; Hedstrom, Lizbeth; Zhuo, Ling; Malkas, Linda H.; Chen, Lifeng; Puchades-Carrasco, Leonor; Wert-Lamas, Leon; Su, Leila; Byrne, Lee J.; Cowen, Leah E.; Haupt, Larisa M.; Lehtio, Lari; Pusztai, Lajos; Lee, Kyung Hyeon; Kim, Kyu Kwang; Rohde, Kyle H.; Sarosiek, Kristopher; Smith, Kristiana S.; Liu, Koting; Korotkov, Konstantin V.; Mostert, Konrad J.; Nagamori, Kiyo; Faller, Kiterie M.E.; Musta, Kirsikka; McManus, Kirk James; Sugamori, Kim S.; Ghilarducci, Kim; Pham, Kien; Machaca, Khaled; Parang, Keykavous; Hopkins, Kevin M.; Lobb, Kevin A.; Lai, Kent; Wentworth, Kelly L.; Wong, Keith S.; Ojo, Kayode K.; Gadar, Kavita; Martin, Katie R.; Cunningham, Kathryn A.; Molyneaux, Kathleen A.; Hansen, Kasper B.; Francisco, Karol R.; Sishtla, Kamakshi; Abrahão, Jônatas Santos; Sistla, Jyothi C.; Liao, Junzhuo; Kee, Jung Min; Wang, Jun; Bogomolovas, Julijus; Lescar, Julien; Cools, Julie; Milosavljevic, Julian; Oyarzabal, Julen; Lasarte, Juan José; Arias, Juan Antonio Sanchez; Rodriguez-Frade, José Miguel; Watkins, Joshua; Finkelstein, Joshua M.; Gruber, Joshua J.; Nasburg, Joshua Alexander; Maciag, Joseph J.; Rayman, Joseph B.; Costoya, Jose A.; Pederick, Jordan L.; So, Jonathan; Pascal, John M.; Tanner, John J.; Coles, John G.; Bruning, John Burt; Bruning, John B.; Stetefeld, Joerg; Reis, Joana; Lee, Jiyoun; Lin, Jiusheng; Zhao, Jinshi; Xu, Jingyi; Liao, Jiayu; Zhu, Jiaqi; Wang, Jianghai; Xu, Jiake; Lin, Jiabei; Zhou, Jia; Jossart, Jennifer N.; MacKeigan, Jeffrey P.; Dickhout, Jeffrey; Evans, Jay D.; Maynes, Jason T.; Mousa, Jarrod J.; Chuah, Janelle; Gebauer, Jan M.; Voss, Jan Hendrik; Shorter, James; Ng, James; Granneman, James G.; Siqueira-Neto, Jair L.; Miner, Jaden; Kratz, Jadel Müller; Fries, Jacob; Ferreira, Jacob; Boorman, Jacob; Kwiatkowski, Jacek; Perry, J. Jefferson P.; Cakir, Isin; Lotsaris, Irina; Qureshi, Insaf Ahmed; Verhamme, Ingrid M.; Mungrue, Imran N.; Arozarena, Imanol; Corvo, Ileana; Caliandro, Ileana; Greig, Iain R.; Kim, Hyeong Jun; Zhou, Hui; Feng, Hui; Fan, Hua Ying; Jung, Hoyoung; Lieberman, Howard B.; Debonsi, Hosana Maria; Xu, Hongyang; Van Remmen, Holly; Tam, Heng Keat; Chaytow, Helena; Hoppe, Heinrich; Wulff, Heike; Shim, Heesung; Yuan, Haynes; Tilford, Hannah; Moore, Hannah P.; Zhou, Han; Jafar-Nejad, Hamed; Breton, Hairol E.; Li, Hai; Cildir, Gokhan; Lee, Gyeongeun; Rucinski, Gwennan; Alvarez, Guzmán; Caljon, Guy; Akk, Gustav; de Souza, Guilherme Eduardo; Veit, Guido; Popowicz, Grzegorz Maria; Bowman, Gregory R.; Stuchbury, Grant David; Conn, Graeme L.; Michlewski, Gracjan; Dahal, Gopal; Leuzzi, Giuseppe; Gasparre, Giuseppe; Fiermonte, Giuseppe; Girolimetti, Giulia; Roti, Giovanni; Cortopassi, Gino; De Keulenaer, Gilles; Colotti, Gianni; Parico, Gian Carlo G.; Prikler, Gergely; Lukacs, Gergely L.; Garcia, George A.; Greene, Geoffrey L.; Mayer, Gaétan; Eitzen, Gary; Dempsey, Garrett; Zhang, Gang; Lembo, Gaia; Bognár, Gabriella; Rodriguez, G. Marcela; Svensson, Fredrik; Bdira, Fredj Ben; Vizeacoumar, Frederick S.; Buckner, Frederick S.; Luh, Frank; Vizeacoumar, Franco J.; Borriello, Francesco; van den Akker, Focco; Ingoglia, Filippo; Wang, Feng; Leng, Fenfei; Xiang, Fei; Yu, Fang; Gavathiotis, Evripidis; Glukhov, Evgenia; Garcia-Cuesta, Eva M.; Jo, Eunji; Kroon, Erna Geessien; Fan, Erkang; Lisabeth, Erika Mathes; Cione, Erika; Thompson, Erik W.; Strauss, Erick; Rubin, Eric J.; Trakhtenberg, Ephraim F.; Petretto, Enrico; Mason, Emily R.; Christensen, Emily M.; Leung, Elisa; Mameli, Eleonora; Lama, Eleonora; Abraham, Elena Theres; Lenci, Elena; Aguilera, Elena; Silva, Elany Barbosa; Lynn, Edward G.; Hsiao, Edward C.; Gelardi, Edoardo Luigi Maria; Glubb, Dylan M.; Duncan, Dustin; Krishnamurthy, Durga; Zochodne, Douglas William; Shoue, Douglas A.; Dirksen, Dorian; Lee, Donghan; Ronning, Donald R.; Slotboom, Dirk J.; Chaudhuri, Dipayan; Zhang, Dingqiang; Alramadhani, Dina; Ortiz, Diana; Hu, Di; Welsbie, Derek S.; Coombe, Deirdre R.; Anderson, Deborah H.; Ferraris, Davide Maria; Riches, David W.H.; Krist, David T.; Shum, David; Siderovski, David P.; Moreira, David; Smith, David M.; Hosfield, David J.; Dowling, David J.; Drewry, David H.; Hildeman, David A.; Trader, Darci J.; Manor, Danny; Chen, Daniel; Lawrence, Daniel A.; Keedy, Daniel A.; Tumes, Damon J.; Luo, Dahai; Santiago, César; Paulino, Cristina; Arrigoni, Cristina; Myhr, Courtney; Wilson, Cornelia M.; Loy, Cody A.; Reglero, Clara; Alkan, Cigdem; Morisseau, Christophe; Muli, Christine S.; Zeina, Christina M.; Weber, Christian; Müller, Christa E.; Kemet, Chinyere Maat; Mantri, Chinmay Kumar; Peltier, Cheryl; Liu, Chen; Huimei, Chen; Dieck, Chelsea L.; Keller, Charles; Karan, Charles; Kahler, Charlene M.; Yang, Chao Yie; Huang, Chang; Chaton, Catherine T.; Partch, Carrie L.; Chapman, Carly J.; Bon, Carlotta; Ballatore, Carlo; Torner, Carles; Novina, Carl D.; Lempicki, Camille; Fraser, Cameron; Dickinson, Bryan C.; Mota, Bruno Eduardo Fernandes; Hammock, Bruce D.; Morten, Brianna C.; Dymock, Brian W.; Geisbrecht, Brian V.; Duggan, Brendan M.; Salas, Brenda P.Medellin; Pressly, Brandon; Agianian, Bogos; Gong, Bin; Balakrishnan, Bijina; Englinger, Bernhard; Kováts, Benjámin; Chua, Benjamin Soon Kai; Perry, Benjamin; Liou, Benjamin; Edelman, Benjamin L.; Bailey-Elkin, Ben A.; Ribeiro, Beatriz Murta Rezende Moraes; Diallo, Bakary N"™tji; O"™Dea, Austin; Colomba, Audrey; Apfel, Athena Marie; ElSheikh, Assmaa; Prince, Ashutosh; John, Ashley L.St; Paparella, Ashleigh S.; Haas, Arthur L.; Chatterjee, Arnab K.; Samantha, Ariela; Panganiban, Antonito T.; Pineda-Lucena, Antonio; Garmendia, Antonio E.; Del Rio Flores, Antonio; O"™Donoghue, Anthony J.; Virtanen, Anniina; Fiorillo, Annarita; Müller, Anna; Montanaro, Anna; Minakova, Anna; Porcelli, Anna Maria; Hirsch, Anna K.H.; D"™Antuono, Anna; Borowska, Anna; Motyl, Anna A.L.; Cathcart, Ann M.; Ojha, Anil K.; Taglialatela, Angelo; White, Andrew; Cuddihy, Andrew R.; Lam, Andrew; Reidenbach, Andrew G.; Freywald, Andrew; Berti, Andrew; Herr, Andrew B.; Stahl, Andreas; Trabocchi, Andrea; Foote, Andrea Talbot; Mattevi, Andrea; Ilari, Andrea; Chini, Andrea; Caporali, Andrea; Battistoni, Andrea; Matheeussen, An; Rangarajan, Amith Vikram; Patel, Amit K.; Caflisch, Amedeo; Bryant-Friedrich, Amanda; Garaeva, Alisa A.; Vrielink, Alice; Tomilov, Alexey; Degterev, Alexei; Gingras, Alexandre R.; Statsyuk, Alexander V.; Freiberg, Alexander N.; Kushnir, Alexander; Agoulnik, Alexander I.; de Sousa, Alessandra Mara; Sverzhinsky, Aleksandr; de Oliveira, Aldo Sena; Ciccia, Alberto; Smrcka, Alan V.; Toh, Alan Kie Leong; Shaqra, Ala M.; Mushtaq, Aisha; Ayachi, Aicha Gharbi; Ghosh, Agnidipta; Andricopulo, Adriano D.; Ferrando, Adolfo A.; Presser, Adam G.; Mysore, Venkatesh; Gupta, Tushita; Abramyan, Tigran M.; Schroedl, Stefan; Pemberton, Ryan P.; DeHaan, Nicholas; Young, Matthew A.; Goldenberg, Joshua M.; Sorenson, Jon M.; Warrington, Jeffrey M.; Cox, Bryan D.; Anderson, Brandon M.; Bergman, Bastiaan; Cann, Andrew B.; Lee, Andreia H.; Kenyon, Victor; Chern, Ting Rong; Williams, Tiffany; Van Grack, Tessa; O"™Brien, Terrence E.; Palazzo, Teresa; Hare, Stephanie; Contreras, Stephanie; Shek, Stefani; PrasadPrasad, Srimukh Veccham Krishna; Suterwala, Shabbir; de Oliveira, Saulo; Eckert, Sam; Gniewek, Pawel; Henriksen, Niel; Anthis, Nicholas J.; Ahmed, Mostafa; Mysinger, Michael; Ngo, Lien; Giesler, Kyle; Sarangapani, Krishna; Stafford, Kate; Ng, Ho Leung; van den Bedem, Henry; Truong, Ha; Friedland, Greg; Moharreri, Ehsan; Thayer, Desiree; Laggner, Christian; Butler, Brittany; Worley, Brad; Thomas, Bill; Samudio, Ben; Davtyan, Aram; O"™Sullivan, Ann Marie; Rosnik, Andreana; Stecula, Adrian; Morrison, Adrian; Ho, Gregory; Nguyen, Kong; Bernard, Denzil; Wallach, Izhar
Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-024-54655-z, published online 02 April 2024 The original version of this Article contained errors. In the original version of this article, Ellie Giles was omitted from the Author list. Additionally, the following Affiliation information has been updated: 1. Affiliation 25 was incorrect. Affiliation 25 "˜Queensland University of Technology, Brisbane, USA."™ now reads, "˜Queensland University of Technology, Brisbane, Australia."™ 2. Marta Giorgis was incorrectly affiliated with the "˜University of Aberdeen, Aberdeen, UK."™ The correct Affiliation is listed below: "˜University of Turin, Turin, Italy."™ 3. Affiliations 52, 125 and 261 were duplicated. As a result, the correct Affiliation for Andrew B. Herr, Benjamin Liou, David A. Hildeman, Joseph J. Maciag, Ying Sun, Durga Krishnamurthy, and Stephen N. Waggoner is: "˜Cincinnati Children"™s Hospital Medical Center, Cincinnati, USA."™ Furthermore, an outdated version of Figure 1 was typeset. The original Figure 1 and accompanying legend appear below. (Figure presented.) Pairs of representative compounds extracted from AI patents (right) and corresponding prior patents (left) for clinical-stage programs (CDK792,93, A2Ar-antagonist94,95, MALT196,97, QPCTL98,99, USP1100,101, and 3CLpro102,103). The identical atoms between the chemical structures are highlighted in red. Lastly, The Acknowledgements section contained an error. "See Supplementary section S1." now reads, "See Supplementary section S2." The original Article has been corrected.
SCOPUS:85204723078
ISSN: 2045-2322
CID: 5714322
VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system
So, Jonathan; Mabe, Nathaniel W; Englinger, Bernhard; Chow, Kin-Hoe; Moyer, Sydney M; Yerrum, Smitha; Trissal, Maria C; Marques, Joana G; Kwon, Jason J; Shim, Brian; Pal, Sangita; Panditharatna, Eshini; Quinn, Thomas; Schaefer, Daniel A; Jeong, Daeun; Mayhew, David L; Hwang, Justin; Beroukhim, Rameen; Ligon, Keith L; Stegmaier, Kimberly; Filbin, Mariella G; Hahn, William C
Collateral lethality occurs when loss of a gene/protein renders cancer cells dependent on its remaining paralog. Combining genome-scale CRISPR/Cas9 loss-of-function screens with RNA sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase vaccinia-related kinase 1 (VRK1) for their survival in vivo. VRK1 dependency was inversely correlated with expression of its paralog VRK2. VRK2 knockout sensitized cells to VRK1 loss, and conversely, VRK2 overexpression increased cell fitness in the setting of VRK1 loss. DNA methylation of the VRK2 promoter was associated with low VRK2 expression in human neuroblastomas and adult and pediatric gliomas. Mechanistically, depletion of VRK1 reduced barrier-to-autointegration factor phosphorylation during mitosis, resulting in DNA damage and apoptosis. Together, these studies identify VRK1 as a synthetic lethal target in VRK2 promoter-methylated adult and pediatric gliomas and neuroblastomas.
PMCID:9675470
PMID: 36040810
ISSN: 2379-3708
CID: 5633432
Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex
Kwon, Jason J; Hajian, Behnoush; Bian, Yuemin; Young, Lucy C; Amor, Alvaro J; Fuller, James R; Fraley, Cara V; Sykes, Abbey M; So, Jonathan; Pan, Joshua; Baker, Laura; Lee, Sun Joo; Wheeler, Douglas B; Mayhew, David L; Persky, Nicole S; Yang, Xiaoping; Root, David E; Barsotti, Anthony M; Stamford, Andrew W; Perry, Charles K; Burgin, Alex; McCormick, Frank; Lemke, Christopher T; Hahn, William C; Aguirre, Andrew J
Receptor tyrosine kinase (RTK)-RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2-MRAS-PP1C holophosphatase complex functions as a key regulator of RTK-RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling1. SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes2-5. However, the structure and assembly of this complex are poorly understood. Here we use cryo-electron microscopy to resolve the structure of the SHOC2-MRAS-PP1C complex. We define the biophysical principles of holoenzyme interactions, elucidate the assembly order of the complex, and systematically interrogate the functional consequence of nearly all of the possible missense variants of SHOC2 through deep mutational scanning. We show that SHOC2 binds PP1C and MRAS through the concave surface of the leucine-rich repeat region and further engages PP1C through the N-terminal disordered region that contains a cryptic RVXF motif. Complex formation is initially mediated by interactions between SHOC2 and PP1C and is stabilized by the binding of GTP-loaded MRAS. These observations explain how mutant versions of SHOC2 in RASopathies and cancer stabilize the interactions of complex members to enhance holophosphatase activity. Together, this integrative structure-function model comprehensively defines key binding interactions within the SHOC2-MRAS-PP1C holophosphatase complex and will inform therapeutic development .
PMID: 35831509
ISSN: 1476-4687
CID: 5633422
CREB5 reprograms FOXA1 nuclear interactions to promote resistance to androgen receptor-targeting therapies
Hwang, Justin H; Arafeh, Rand; Seo, Ji-Heui; Baca, Sylvan C; Ludwig, Megan; Arnoff, Taylor E; Sawyer, Lydia; Richter, Camden; Tape, Sydney; Bergom, Hannah E; McSweeney, Sean; Rennhack, Jonathan P; Klingenberg, Sarah A; Cheung, Alexander T M; Kwon, Jason; So, Jonathan; Kregel, Steven; Van Allen, Eliezer M; Drake, Justin M; Freedman, Matthew L; Hahn, William C
Metastatic castration-resistant prostate cancers (mCRPCs) are treated with therapies that antagonize the androgen receptor (AR). Nearly all patients develop resistance to AR-targeted therapies (ARTs). Our previous work identified CREB5 as an upregulated target gene in human mCRPC that promoted resistance to all clinically approved ART. The mechanisms by which CREB5 promotes progression of mCRPC or other cancers remains elusive. Integrating ChIP-seq and rapid immunoprecipitation and mass spectroscopy of endogenous proteins, we report that cells overexpressing CREB5 demonstrate extensive reprogramming of nuclear protein-protein interactions in response to the ART agent enzalutamide. Specifically, CREB5 physically interacts with AR, the pioneering actor FOXA1, and other known co-factors of AR and FOXA1 at transcription regulatory elements recently found to be active in mCRPC patients. We identified a subset of CREB5/FOXA1 co-interacting nuclear factors that have critical functions for AR transcription (GRHL2, HOXB13) while others (TBX3, NFIC) regulated cell viability and ART resistance and were amplified or overexpressed in mCRPC. Upon examining the nuclear protein interactions and the impact of CREB5 expression on the mCRPC patient transcriptome, we found that CREB5 was associated with Wnt signaling and epithelial to mesenchymal transitions, implicating these pathways in CREB5/FOXA1-mediated ART resistance. Overall, these observations define the molecular interactions among CREB5, FOXA1, and pathways that promote ART resistance.
PMCID:9135408
PMID: 35550030
ISSN: 2050-084x
CID: 5633412
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics
Bekele, Raie T; Samant, Amruta S; Nassar, Amin H; So, Jonathan; Garcia, Elizabeth P; Curran, Catherine R; Hwang, Justin H; Mayhew, David L; Nag, Anwesha; Thorner, Aaron R; Börcsök, Judit; Sztupinszki, Zsofia; Pan, Chong-Xian; Bellmunt, Joaquim; Kwiatkowski, David J; Sonpavde, Guru P; Van Allen, Eliezer M; Mouw, Kent W
Bladder cancer is a genetically heterogeneous disease, and novel therapeutic strategies are needed to expand treatment options and improve clinical outcomes. Here, we identified a unique subset of urothelial tumors with focal amplification of the RAF1 (CRAF) kinase gene. RAF1-amplified tumors had activation of the RAF/MEK/ERK signaling pathway and exhibited a luminal gene expression pattern. Genetic studies demonstrated that RAF1-amplified tumors were dependent upon RAF1 activity for survival, and RAF1-activated cell lines and patient-derived models were sensitive to available and emerging RAF inhibitors as well as combined RAF plus MEK inhibition. Furthermore, we found that bladder tumors with HRAS- or NRAS-activating mutations were dependent on RAF1-mediated signaling and were sensitive to RAF1-targeted therapy. Together, these data identified RAF1 activation as a dependency in a subset making up nearly 20% of urothelial tumors and suggested that targeting RAF1-mediated signaling represents a rational therapeutic strategy.
PMID: 34554931
ISSN: 1558-8238
CID: 5633402
Transcription factor networks of oligodendrogliomas treated with adjuvant radiotherapy or observation inform prognosis
So, Jonathan; Mamatjan, Yasin; Zadeh, Gelareh; Aldape, Kenneth; Moraes, Fabio Y
BACKGROUND:Recent international sequencing efforts have allowed for the molecular taxonomy of lower-grade gliomas (LGG). We sought to analyze The Cancer Genome Atlas (TCGA, 2015) gene expression datasets on molecularly defined oligodendrogliomas (IDH-mutated and 1p/19q-codeleted) patients treated with adjuvant radiation or those observed to discover prognostic markers and pathways. METHODS:mRNA expression and clinical information of patients with oligodendroglioma were taken from the TCGA "Brain Lower Grade Glioma" provisional dataset. Transcription factor network reconstruction and analysis were performed using the R packages "RTN" and "RTNsurvival." Elastic net regularization and survival modeling were performed using the "biospear," "plsRCox," "survival" packages. RESULTS:From our cohort of 137 patients, 65 received adjuvant radiation and 72 were observed. In the cohort that received adjuvant radiotherapy, a transcription factor activity signature, that correlated with hypoxia, was associated with shorter disease-free survival (DFS) (median = 45 months vs 108 months, P < .001). This increased risk was not seen in patients who were observed (P = .2). Within the observation cohort, a transcription factor activity signature was generated that was associated with poor DFS (median = 72 months. vs 143 months., P < .01). CONCLUSIONS:We identified a transcription factor activity signature associated with poor prognosis in patients with molecular oligodendroglioma treated with adjuvant radiotherapy. These patients would be potential candidates for treatment intensification. A second signature was generated for patients who were more likely to progress on observation. This potentially identifies a cohort who would benefit from upfront adjuvant radiotherapy.
PMCID:8099467
PMID: 33367753
ISSN: 1523-5866
CID: 5633392
