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

1. Nat Methods. 2017 Jun;14(6):573-576. doi: 10.1038/nmeth.4225. Epub 2017 Mar 20. Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. Shen JP(1)(2)(3), Zhao D(3)(4), Sasik R(5), Luebeck J(6), Birmingham A(5), Bojorquez-Gomez A(1), Licon K(1), Klepper K(1), Pekin D(1), Beckett AN(1), Sanchez KS(1), Thomas A(6)(7), Kuo CC(4)(7), Du D(3)(8), Roguev A(3)(9), Lewis NE(7)(10), Chang AN(5), Kreisberg JF(1)(3), Krogan N(3)(9), Qi L(3)(11), Ideker T(1)(2)(3)(5), Mali P(2)(3)(4). Author information: (1)Department of Medicine, Division of Genetics, University of California, San Diego, La Jolla, California, USA. (2)Moores UCSD Cancer Center, La Jolla, California, USA. (3)The Cancer Cell Map Initiative (CCMI), La Jolla and San Francisco, California, USA. (4)Department of Bioengineering, University of California, San Diego, La Jolla, California, USA. (5)Center for Computational Biology &Bioinformatics, University of California, San Diego, La Jolla, California, USA. (6)Bioinformatics &Systems Biology Program, University of California, San Diego, La Jolla, California, USA. (7)Novo Nordisk Center for Biosustainability at the University of California, San Diego, La Jolla, California, USA. (8)Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, California, USA. (9)Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA. (10)Department of Pediatrics, University of California, San Diego, La Jolla, California, USA. (11)Department of Bioengineering, Stanford University, Stanford, California, USA. Comment in Nat Rev Genet. 2017 May;18(5):272-273. doi: 10.1038/nrg.2017.25. 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. DOI: 10.1038/nmeth.4225 PMCID: PMC5449203 PMID: 28319113 [Indexed for MEDLINE] Conflict of interest statement: Competing financial interests. All authors report no competing financial interests.