Minimal genome-wide human CRISPR-Cas9 library

被引:36
|
作者
Goncalves, Emanuel [1 ]
Thomas, Mark [1 ]
Behan, Fiona M. [1 ]
Picco, Gabriele [1 ]
Pacini, Clare [1 ,2 ]
Allen, Felicity [1 ]
Vinceti, Alessandro [3 ]
Sharma, Mamta [1 ]
Jackson, David A. [1 ]
Price, Stacey [1 ]
Beaver, Charlotte M. [1 ]
Dovey, Oliver [1 ]
Parry-Smith, David [1 ]
Iorio, Francesco [1 ,3 ]
Parts, Leopold [1 ,4 ]
Yusa, Kosuke [5 ]
Garnett, Mathew J. [1 ]
机构
[1] Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton, England
[2] Open Targets, Wellcome Genome Campus, Cambridge CB10 1SA, England
[3] Human Technopole, Via Cristina Belgioioso 147, I-20157 Milan, Italy
[4] Univ Tartu, Dept Comp Sci, 18 Narva St, Tartu, Estonia
[5] Kyoto Univ, Inst Frontier Life & Med Sci, Kyoto 6068507, Japan
基金
英国惠康基金;
关键词
CRISPR-Cas9; Genome-wide; Minimal library; Organoid; KS score; GENETIC SCREENS; DRUG-SENSITIVITY; POOLED LIBRARY; KNOCKOUT; DESIGN; VULNERABILITIES; IDENTIFICATION; SPECIFICITY; DISCOVERY; TARGETS;
D O I
10.1186/s13059-021-02268-4
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
CRISPR guide RNA libraries have been iteratively improved to provide increasingly efficient reagents, although their large size is a barrier for many applications. We design an optimised minimal genome-wide human CRISPR-Cas9 library (MinLibCas9) by mining existing large-scale gene loss-of-function datasets, resulting in a greater than 42% reduction in size compared to other CRISPR-Cas9 libraries while preserving assay sensitivity and specificity. MinLibCas9 provides backward compatibility with existing datasets, increases the dynamic range of CRISPR-Cas9 screens and extends their application to complex models and assays.
引用
收藏
页数:14
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