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

ABSTRACT: 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.

SUBMITTER: Shen JP

PROVIDER: S-EPMC5449203 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Shen John Paul JP Zhao Dongxin D Sasik Roman R Luebeck Jens J Birmingham Amanda A Bojorquez-Gomez Ana A Licon Katherine K Klepper Kristin K Pekin Daniel D Beckett Alex N AN Sanchez Kyle Salinas KS Thomas Alex A Kuo Chih-Chung CC Du Dan D Roguev Assen A Lewis Nathan E NE Chang Aaron N AN Kreisberg Jason F JF Krogan Nevan N Qi Lei L Ideker Trey T Mali Prashant P

Nature methods 20170320 6

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 syntheti ...[more]

PMID: 28319113

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