机构：[1]State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200432, China.[2]Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.[3]Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, China.[4]Human Phenome Institute, Fudan University, Shanghai 200438, China.[5]Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China.首都医科大学附属安贞医院
Highly specific Cas9 nucleases derived from SpCas9 are valuable tools for genome editing, but their wide applications are hampered by a lack of knowledge governing guide RNA (gRNA) activity. Here, we perform a genome-scale screen to measure gRNA activity for two highly specific SpCas9 variants (eSpCas9(1.1) and SpCas9-HF1) and wild-type SpCas9 (WT-SpCas9) in human cells, and obtain indel rates of over 50,000 gRNAs for each nuclease, covering ~20,000 genes. We evaluate the contribution of 1,031 features to gRNA activity and develope models for activity prediction. Our data reveals that a combination of RNN with important biological features outperforms other models for activity prediction. We further demonstrate that our model outperforms other popular gRNA design tools. Finally, we develop an online design tool DeepHF for the three Cas9 nucleases. The database, as well as the designer tool, is freely accessible via a web server, http://www.DeepHF.com/ .
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81870199, 31720103909, 31471239]; National Basic Research Program of ChinaNational Basic Research Program of China [2015CB943300]; Foundation for Innovative Research Group of the National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31521003]; National Key R&D Project of China [2016YFC0901704, 2017YFC0907502]; Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]; State Key Laboratory Opening Program [SKLGE1809]
第一作者机构：[1]State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200432, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200432, China.[5]Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China.
推荐引用方式(GB/T 7714)：
Daqi Wang,Chengdong Zhang,Bei Wang,et al.Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning[J].NATURE COMMUNICATIONS.2019,10(1):4284.doi:10.1038/s41467-019-12281-8.
APA：
Daqi Wang,Chengdong Zhang,Bei Wang,Bin Li,Qiang Wang...&Yongming Wang.(2019).Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning.NATURE COMMUNICATIONS,10,(1)
MLA：
Daqi Wang,et al."Optimized CRISPR guide RNA design for two high-fidelity Cas9 variants by deep learning".NATURE COMMUNICATIONS 10..1(2019):4284
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