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Prediction of the sequence-specific cleavage activity of Cas9 variants

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Title
Prediction of the sequence-specific cleavage activity of Cas9 variants
Author(s)
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
Subject
CRISPR-CAS9 NUCLEASES, ; HUMAN-CELLS, ; GENOME, ; DESIGN, ; DNA, ; SCREENS, ; DROPOUT, ; SPCAS9
Publication Date
2020-11
Journal
NATURE BIOTECHNOLOGY, v.38, pp.1328 - 1336
Publisher
NATURE PUBLISHING GROUP
Abstract
© The Author(s), under exclusive licence to Springer Nature America, Inc. 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 approximate to xCas9 >> evoCas9, whereas their overall specificities could be ranked as evoCas9 >> HypaCas9 >= SpCas9-HF1 approximate to 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
URI
https://pr.ibs.re.kr/handle/8788114/8452
DOI
10.1038/s41587-020-0537-9
ISSN
1087-0156
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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