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

被引：249

作者：

Shen, John Paul ^{[1
,2
,3
,4
]}

Zhao, Dongxin ^{[3
,4
,5
]}

Sasik, Roman ^{[6
]}

Luebeck, Jens ^{[7
]}

Birmingham, Amanda ^{[6
]}

Bojorquez-Gomez, Ana ^{[1
]}

Licon, Katherine ^{[1
]}

Klepper, Kristin ^{[1
]}

Pekin, Daniel ^{[1
]}

Beckett, Alex N. ^{[1
]}

Sanchez, Kyle Salinas ^{[1
]}

Thomas, Alex ^{[7
,8
]}

Kuo, Chih-Chung ^{[5
]}

Du, Dan ^{[3
,4
,9
]}

Roguev, Assen ^{[3
,4
,10
]}

Lewis, Nathan E. ^{[8
,11
]}

Chang, Aaron N. ^{[6
]}

Kreisberg, Jason F. ^{[1
,3
,4
]}

Krogan, Nevan ^{[3
,4
,10
]}

Qi, Lei ^{[3
,4
,12
]}

Ideker, Trey ^{[1
,2
,3
,4
,6
]}

Mali, Prashant ^{[2
,3
,4
,5
]}

机构：

[1] Univ Calif San Diego, Dept Med, Div Genet, La Jolla, CA 92093 USA

[2] Moores UCSD Canc Ctr, La Jolla, CA 92093 USA

[3] Canc Cell Map Initiat, La Jolla, CA 92037 USA

[4] Canc Cell Map Initiat, San Francisco, CA 94143 USA

[5] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Ctr Computat Biol & Bioinformat, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Novo Nordisk Ctr Biosustainabil, La Jolla, CA 92093 USA

[9] Univ Calif San Francisco, Dept Cell & Tissue Biol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA

[11] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[12] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

来源：

NATURE METHODS | 2017年 / 14卷 / 06期

关键词：

FALSE DISCOVERY RATE; NETWORKS; CAS9; FITNESS; YEAST;

D O I：

10.1038/nmeth.4225

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：573 / +

页数：9

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