Journal
NATURE METHODS
Volume 14, Issue 6, Pages 573-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nmeth.4225
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Funding
- UC San Diego School of Engineering and School of Medicine institutional funds
- Burroughs Wellcome Fund [1013926]
- March of Dimes Foundation [5-FY15-450]
- Sidney Kimmel Foundation [SKF-16-150]
- California Institute for Regenerative Medicine
- National Cancer Institute [R21 CA199292, L30 CA171000]
- National Institute for Environmental Health Sciences [R01 ES014811]
- National Institute for General Medical Sciences [T32 GM008806, RO1 GM084279, P50 GM085764]
- UC San Diego Clinical and Translational Research Institute Grant [UL1TR001442]
- Novo Nordisk Foundation Center for Biosustainability at DTU [NNF16CC0021858]
- NNF Center for Biosustainability [CHO in Silico Protein Quality Engin] Funding Source: researchfish
- Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish
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We developed a systematic approach to map human genetic networks by combinatorial CRISPR Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies.
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