Shen2017

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

• Shen, J. P. et al. Nat. Methods 14, 573–576, 2017. 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, altogether comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified and these patterns replicated with combinatorial drugs at 75% precision. A total of 152 synthetic-lethal (negative) genetic interactions were identified in either HeLa, A549, or 293T cells (FDR ~ 0.3, Fig. 2D, Supplementary Fig. 6A–C, Supplementary Table S3B,C).