1. Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening
- Author
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Christine Stephan, William R. Sellers, Deborah Castelletti, Jeffery A. Porter, Julie L. Bernard, Sandra Mollé, Mark Stump, Tami Hood, Joshua M. Korn, Audrey Kauffmann, Giorgio G. Galli, Kristine Yu, Li Li, Marc Hattenberger, Javad Golji, Zainab Jagani, Marco Wallroth, Tobias Schmelzle, Philippe Megel, Raymond Pagliarini, Rosemary Barrett, Yingzi Yue, Richard S. Eldridge, Jan Weiler, Alberto C. Vitari, Konstantinos J. Mavrakis, Kalyani Gampa, Elizabeth Ackley, Rosalie deBeaumont, Qiong Shen, Joel Berger, Tanja Schouwey, Franklin Chung, E. Robert McDonald, Gregory McAllister, Christelle Stamm, Frances Shanahan, Aurore Desplat, Iris Kao, Thomas A. Perkins, Antoine de Weck, Kavitha Venkatesan, Albert Lai, Jennifer Johnson, Roland Widmer, David A. Ruddy, Avnish Kapoor, Brian Repko, François Gauter, Nicholas Keen, Tanushree Phadke, Eric Billy, Sosathya Sovath, Typhaine Martin, Elizabeth Frias, Justina X. Caushi, Vic E. Myer, Malini Varadarajan, William C. Forrester, Fei Feng, Hans Bitter, Ralph Tiedt, Yue Liu, Jing Zhang, Dorothee Abramowski, Dhiren Belur, Volker M. Stucke, Odile Weber, Mathias Jenal, Ali Farsidjani, Jianjun Yu, Rebecca Billig, JiaJia Feng, A. B. Meyer, Kristen Hurov, Veronica Gibaja, Michael D. Jones, Daisy Flemming, Donald A. Dwoske, Jilin Liu, Clara Delaunay, William Duong, Frank Buxton, Kaitlin J. Macchi, Saskia M. Brachmann, Alice T. Loo, Craig Mickanin, Francesco Hofmann, Frank Stegmeier, Kristy Haas, Gregory R. Hoffman, Marta Cortes-Cros, Roger Caothien, Shumei Liu, Serena J. Silver, Michael R. Schlabach, Emma Lees, Nadire Ramadan, Qiumei Liu, and Zhenhai Gao
- Subjects
0301 basic medicine ,Lineage (genetic) ,Tumor suppressor gene ,Mutant ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,RNA interference ,Cell Line, Tumor ,Neoplasms ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Small Interfering ,Gene ,Gene Library ,Genetics ,Gene knockdown ,Cancer ,Translation (biology) ,Oncogenes ,medicine.disease ,030104 developmental biology ,Multiprotein Complexes ,RNA Interference ,Signal Transduction ,Transcription Factors - Abstract
Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.
- Published
- 2017
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