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基于混合神经网络的CRISPR-Cas9靶向活性预测

Prediction of CRISPR-Cas9 on-target activity based on a hybrid neural network.

作者信息

Li Chuxuan, Zou Quan, Li Jian, Feng Hailin

机构信息

School of Mathematics and Computer science, Zhejiang A&F University, Hangzhou 311300, China.

Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou 324000, China.

出版信息

Comput Struct Biotechnol J. 2025 May 27;27:2098-2106. doi: 10.1016/j.csbj.2025.05.001. eCollection 2025.

DOI:10.1016/j.csbj.2025.05.001
PMID:40502933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12153376/
Abstract

CRISPR-Cas9 is a groundbreaking gene editing technology, but variations in targeted editing efficiency arise due to significant discrepancies in sgRNA activity. Therefore, improving the prediction accuracy of sgRNA activity is crucial for its safety and effectiveness. Deep learning methods have surpassed traditional scoring and machine learning methods, demonstrating higher prediction accuracy and scalability. However, challenges persist in local feature extraction, cross-sequence dependency modeling, and dynamic feature weight assignment. To address these issues, we introduce CRISPR_HNN, a hybrid deep neural network model that integrates MSC, MHSA, and BiGRU to effectively capture local dynamic features and global long-distance dependencies. In addition, it adopts One-hot Encoding and Label Encoding strategies. Experimental results demonstrate that CRISPR_HNN surpasses existing models on public datasets and substantially enhances the accuracy of sgRNA activity prediction.

摘要

CRISPR-Cas9是一种开创性的基因编辑技术,但由于sgRNA活性存在显著差异,导致靶向编辑效率出现变化。因此,提高sgRNA活性的预测准确性对其安全性和有效性至关重要。深度学习方法已超越传统评分和机器学习方法,展现出更高的预测准确性和可扩展性。然而,在局部特征提取、跨序列依赖性建模和动态特征权重分配方面仍存在挑战。为解决这些问题,我们引入了CRISPR_HNN,这是一种混合深度神经网络模型,它集成了MSC、MHSA和BiGRU,以有效捕获局部动态特征和全局长距离依赖性。此外,它采用了独热编码和标签编码策略。实验结果表明,CRISPR_HNN在公共数据集上超越了现有模型,并大幅提高了sgRNA活性预测的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/af4df8916813/gr006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/ca090d5b23c7/gr001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/02ba07c86fef/gr002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/ce10c828f2d3/gr003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/c0443fd4324b/gr004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/7808a7f91bc0/gr005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/af4df8916813/gr006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/ca090d5b23c7/gr001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/02ba07c86fef/gr002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/ce10c828f2d3/gr003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/c0443fd4324b/gr004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/7808a7f91bc0/gr005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e7a/12153376/af4df8916813/gr006.jpg

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本文引用的文献

1
DeepMEns: an ensemble model for predicting sgRNA on-target activity based on multiple features.DeepMEns:一种基于多种特征预测sgRNA靶向活性的集成模型。
Brief Funct Genomics. 2025 Jan 15;24. doi: 10.1093/bfgp/elae043.
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Overcoming CRISPR-Cas9 off-target prediction hurdles: A novel approach with ESB rebalancing strategy and CRISPR-MCA model.克服 CRISPR-Cas9 脱靶预测障碍:一种新的方法,结合 ESB 再平衡策略和 CRISPR-MCA 模型。
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CrnnCrispr: An Interpretable Deep Learning Method for CRISPR/Cas9 sgRNA On-Target Activity Prediction.
CrnnCrispr:一种用于CRISPR/Cas9 sgRNA靶向活性预测的可解释深度学习方法。
Int J Mol Sci. 2024 Apr 17;25(8):4429. doi: 10.3390/ijms25084429.
4
Prediction of CRISPR-Cas9 off-target activities with mismatches and indels based on hybrid neural network.基于混合神经网络的具有错配和插入缺失的CRISPR-Cas9脱靶活性预测
Comput Struct Biotechnol J. 2023 Oct 16;21:5039-5048. doi: 10.1016/j.csbj.2023.10.018. eCollection 2023.
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Using traditional machine learning and deep learning methods for on- and off-target prediction in CRISPR/Cas9: a review.基于传统机器学习和深度学习方法的 CRISPR/Cas9 脱靶和靶标预测:综述。
Brief Bioinform. 2023 May 19;24(3). doi: 10.1093/bib/bbad131.
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CRISPR/Cas9 therapeutics: progress and prospects.CRISPR/Cas9 疗法:进展与展望。
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First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.腺相关病毒(AAV)-锌指核酸酶体内基因编辑治疗黏多糖贮积症 I/II 型和血友病 B 的首次人体临床试验。
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