Abstract

The design of CRISPR gRNAs requires accurate on-target efficiency predictions, which demand high-quality gRNA activity data and efficient modeling. To advance, we here report on the generation of on-target gRNA activity data for 10,592 SpCas9 gRNAs. Integrating these with complementary published data, we train a deep learning model, CRISPRon, on 23,902 gRNAs. Compared to existing tools, CRISPRon exhibits significantly higher prediction performances on four test datasets not overlapping with training data used for the development of these tools. Furthermore, we present an interactive gRNA design webserver based on the CRISPRon standalone software, both available via https://rth.dk/resources/crispr/. CRISPRon advances CRISPR applications by providing more accurate gRNA efficiency predictions than the existing tools.

High-quality gRNA activity data is needed for accurate on-target efficiency predictions. Here the authors generate activity data for over 10,000 gRNA and build a deep learning model CRISPRon for improved performance predictions.

Details

Title
Enhancing CRISPR-Cas9 gRNA efficiency prediction by data integration and deep learning
Author
Xiang Xi 1 ; Corsi, Giulia I 2   VIAFID ORCID Logo  ; Anthon Christian 2 ; Qu Kunli 3 ; Pan Xiaoguang 4 ; Xue, Liang 3 ; Han, Peng 3 ; Dong Zhanying 4 ; Liu, Lijun 4 ; Zhong Jiayan 5 ; Ma, Tao 5 ; Wang, Jinbao 5 ; Zhang, Xiuqing 6 ; Jiang, Hui 5 ; Xu Fengping 7 ; Liu, Xin 6   VIAFID ORCID Logo  ; Xu, Xun 8   VIAFID ORCID Logo  ; Wang, Jian 6 ; Yang Huanming 9 ; Bolund Lars 10 ; Church, George M 11 ; Lin, Lin 12   VIAFID ORCID Logo  ; Gorodkin, Jan 2 ; Luo Yonglun 13   VIAFID ORCID Logo 

 Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
 University of Copenhagen, Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, Frederiksberg, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
 Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.5254.6); University of Copenhagen, Department of Biology, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
 Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.5254.6) 
 MGI, BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839) 
 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839) 
 Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.21155.32); BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839) 
 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839) 
 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839) 
10  Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.21155.32); BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
11  Blavatnik Institute, Harvard Medical School, Department of Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
12  Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.38142.3c); Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Steno Diabetes Center Aarhus, Aarhus University, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
13  Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China (GRID:grid.5254.6); BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Steno Diabetes Center Aarhus, Aarhus University, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2533559136
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.