Annotation and evaluation of base editing outcomes in multiple cell types using CRISPRbase
文献类型： 外文期刊
作者： Fan, Jibiao 1 ; Shi, Leisheng 1 ; Liu, Qi 4 ; Zhu, Zhipeng 1 ; Wang, Fan 2 ; Song, Runxian 4 ; Su, Jimeng 2 ; Zhou, Degui 4 ; Chen, Xiao 8 ; Li, Kailong 9 ; Xue, Lixiang 1 ; Sun, Lichao 10 ; Mao, Fengbiao 1 ;
作者机构： 1.Peking Univ Third Hosp, Inst Med Innovat & Res, Beijing 100191, Peoples R China
2.Yangzhou Univ, Coll Anim Sci & Technol, Yangzhou 225009, Jiangsu, Peoples R China
3.Peking Univ Third Hosp, Canc Ctr, Beijing 100191, Peoples R China
4.Guangdong Acad Agr Sci, Rice Res Inst, Guangzhou 510640, Peoples R China
5.Guangdong Key Lab New Technol Rice Breeding, Guangzhou 510640, Peoples R China
6.Guangdong Rice Engn Lab, Guangzhou 510640, Peoples R China
7.Northeast Forestry Univ, Coll Forestry, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China
8.Shandong Univ, Marine Coll, Lab Marine Protozoan Biodivers & Evolut, Weihai 264209, Peoples R China
9.Peking Univ, Sch Basic Med Sci, Dept Biochem & Biophys, Hlth Sci Ctr, Beijing 100191, Peoples R China
10.Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China
期刊名称：NUCLEIC ACIDS RESEARCH （ 影响因子：19.16； 五年影响因子：17.21 ）
ISSN： 0305-1048
年卷期：
页码：
收录情况： SCI
摘要： CRISPR-Cas base editing (BE) system is a powerful tool to expand the scope and efficiency of genome editing with single-nucleotide resolution. The editing efficiency, product purity, and off-target effect differ among various BE systems. Herein, we developed CRISPRbase (http://crisprbase.maolab.org), by integrating 1 252 935 records of base editing outcomes in more than 50 cell types from 17 species. CRISPRbase helps to evaluate the putative editing precision of different BE systems by integrating multiple annotations, functional predictions and a blasting system for single-guide RNA sequences. We systematically assessed the editing window, editing efficiency and product purity of various BE systems. Intensive efforts were focused on increasing the editing efficiency and product purity of base editors since the byproduct could be detrimental in certain applications. Remarkably, more than half of cancer-related off-target mutations were non-synonymous and extremely damaging to protein functions in most common tumor types. Luckily, most of these cancer-related mutations were passenger mutations (4840/5703, 84.87%) rather than cancer driver mutations (863/5703, 15.13%), indicating a weak effect of off-target mutations on carcinogenesis. In summary, CRISPRbase is a powerful and convenient tool to study the outcomes of different base editors and help researchers choose appropriate BE designs for functional studies.
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