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Prediction of the sequence-specific cleavage activity of Cas9 variants

Authors
 Nahye Kim  ;  Hui Kwon Kim  ;  Sungtae Lee  ;  Jung Hwa Seo  ;  Jae Woo Choi  ;  Jinman Park  ;  Seonwoo Min  ;  Sungroh Yoon  ;  Sung-Rae Cho  ;  Hyongbum Henry Kim 
Citation
 NATURE BIOTECHNOLOGY, Vol.38(11) : 1328-1336, 2020-11 
Journal Title
 NATURE BIOTECHNOLOGY 
ISSN
 1087-0156 
Issue Date
2020-11
Abstract
Several Streptococcus pyogenes Cas9 (SpCas9) variants have been developed to improve an enzyme's specificity or to alter or broaden its protospacer-adjacent motif (PAM) compatibility, but selecting the optimal variant for a given target sequence and application remains difficult. To build computational models to predict the sequence-specific activity of 13 SpCas9 variants, we first assessed their cleavage efficiency at 26,891 target sequences. We found that, of the 256 possible four-nucleotide NNNN sequences, 156 can be used as a PAM by at least one of the SpCas9 variants. For the high-fidelity variants, overall activity could be ranked as SpCas9 ≥ Sniper-Cas9 > eSpCas9(1.1) > SpCas9-HF1 > HypaCas9 ≈ xCas9 >> evoCas9, whereas their overall specificities could be ranked as evoCas9 >> HypaCas9 ≥ SpCas9-HF1 ≈ eSpCas9(1.1) > xCas9 > Sniper-Cas9 > SpCas9. Using these data, we developed 16 deep-learning-based computational models that accurately predict the activity of these variants at any target sequence.
Full Text
https://www.nature.com/articles/s41587-020-0537-9
DOI
10.1038/s41587-020-0537-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
Kim, Hui Kwon(김희권)
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180544
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