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

John Paul Shen; Dongxin Zhao; Roman Sasik; Jens Luebeck; Amanda Birmingham; Ana Bojorquez-Gomez; Katherine Licon; Kristin Klepper; Daniel Pekin; Alex N. Beckett; Kyle Salinas Sanchez; Alex Thomas; Chih Chung Kuo; Dan Du; Assen Roguev; Nathan E. Lewis; Aaron N. Chang; Jason F. Kreisberg; Nevan Krogan; Lei Qi; Trey Ideker; Prashant Mali

doi:10.1038/nmeth.4225

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

John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N. Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih Chung Kuo, Dan Du, Assen Roguev, Nathan E. Lewis, Aaron N. Chang, Jason F. Kreisberg, Nevan Krogan, Lei QiTrey Ideker, Prashant Mali

Research output: Contribution to journal › Article › peer-review

242 Scopus citations

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.

Original language	English (US)
Pages (from-to)	573-576
Number of pages	4
Journal	Nature Methods
Volume	14
Issue number	6
DOIs	https://doi.org/10.1038/nmeth.4225
State	Published - May 30 2017
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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Shen, J. P., Zhao, D., Sasik, R., Luebeck, J., Birmingham, A., Bojorquez-Gomez, A., Licon, K., Klepper, K., Pekin, D., Beckett, A. N., Sanchez, K. S., Thomas, A., Kuo, C. C., Du, D., Roguev, A., Lewis, N. E., Chang, A. N., Kreisberg, J. F., Krogan, N., ... Mali, P. (2017). Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. Nature Methods, 14(6), 573-576. https://doi.org/10.1038/nmeth.4225

Shen, JP, Zhao, D, Sasik, R, Luebeck, J, Birmingham, A, Bojorquez-Gomez, A, Licon, K, Klepper, K, Pekin, D, Beckett, AN, Sanchez, KS, Thomas, A, Kuo, CC, Du, D, Roguev, A, Lewis, NE, Chang, AN, Kreisberg, JF, Krogan, N, Qi, L, Ideker, T & Mali, P 2017, 'Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions', Nature Methods, vol. 14, no. 6, pp. 573-576. https://doi.org/10.1038/nmeth.4225

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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.",

author = "Shen, {John Paul} and Dongxin Zhao and Roman Sasik and Jens Luebeck and Amanda Birmingham and Ana Bojorquez-Gomez and Katherine Licon and Kristin Klepper and Daniel Pekin and Beckett, {Alex N.} and Sanchez, {Kyle Salinas} and Alex Thomas and Kuo, {Chih Chung} and Dan Du and Assen Roguev and Lewis, {Nathan E.} and Chang, {Aaron N.} and Kreisberg, {Jason F.} and Nevan Krogan and Lei Qi and Trey Ideker and Prashant Mali",

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AU - Sasik, Roman

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AU - Birmingham, Amanda

AU - Bojorquez-Gomez, Ana

AU - Licon, Katherine

AU - Klepper, Kristin

AU - Pekin, Daniel

AU - Beckett, Alex N.

AU - Sanchez, Kyle Salinas

AU - Thomas, Alex

AU - Kuo, Chih Chung

AU - Du, Dan

AU - Roguev, Assen

AU - Lewis, Nathan E.

AU - Chang, Aaron N.

AU - Kreisberg, Jason F.

AU - Krogan, Nevan

AU - Qi, Lei

AU - Ideker, Trey

AU - Mali, Prashant

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

Abstract

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