Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
John Paul ShenDongxin ZhaoRoman SasikJens LuebeckAmanda BirminghamAna Bojorquez-GomezKatherine LiconKristin KlepperDaniel PekinAlex N BeckettKyle Salinas SanchezAlex ThomasChih-Chung KuoDan DuAssen RoguevNathan E LewisAaron N ChangJason F KreisbergNevan KroganLei S QiTrey IdekerPrashant MaliPublished in: Nature methods (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, 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.
Keyphrases
- crispr cas
- genome wide
- genome editing
- dna methylation
- endothelial cells
- papillary thyroid
- copy number
- high density
- high resolution
- high throughput
- induced pluripotent stem cells
- squamous cell
- cancer therapy
- squamous cell carcinoma
- gene expression
- pluripotent stem cells
- mass spectrometry
- genome wide identification
- childhood cancer
- aqueous solution