Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening
Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening
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DOI：
10.1016/j.cell.2017.07.005
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发表时间：
2017-07-27
期刊：
影响因子：
64.5
通讯作者：
Sellers, William R.
中科院分区：
文献类型：
--
作者：
McDonald, E. Robert, III;de Weck, Antoine;Sellers, William R.
人类癌症的突变景观的阐明进展迅速，并伴随着治疗的发展靶向突变癌基因。然而，对癌症依赖性的全面定位滞后，需要发现对抗肿瘤抑制基因丢失的治疗靶点。为了确定与特定癌症亚型相关的脆弱性，我们进行了大规模的RNAi筛选，在398个癌细胞系中，使用平均每个基因20个shrna来评估mRNA敲低对7,837个基因的活力影响。我们描述了这一筛选的发现，概述了癌症依赖基因的类别及其与遗传、表达和谱系特征的关系。此外，我们还描述了强大的基因相互作用网络，概括了蛋白质复合物和复合物和途径之间的功能合作。该数据集连同门户网站一起提供给社区，以协助发现和翻译新的癌症治疗方法。
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.