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Caps-ac4C:一种基于深度学习识别人类mRNA中N4-乙酰胞苷位点的有效计算框架。

Caps-ac4C: An effective computational framework for identifying N4-acetylcytidine sites in human mRNA based on deep learning.

作者信息

Yao Lantian, Xie Peilin, Dong Danhong, Guo Yilin, Guan Jiahui, Zhang Wenyang, Chung Chia-Ru, Zhao Zhihao, Chiang Ying-Chih, Lee Tzong-Yi

机构信息

Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, 518172 Shenzhen, China; School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, 518172 Shenzhen, China.

Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, 518172 Shenzhen, China; School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, 518172 Shenzhen, China.

出版信息

J Mol Biol. 2025 Mar 15;437(6):168961. doi: 10.1016/j.jmb.2025.168961. Epub 2025 Jan 28.

Abstract

N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer. Therefore, accurately identifying ac4C in human mRNA is essential for gaining deeper insights into disease pathogenesis and provides potential pathways for the development of novel medical interventions. In silico methods for identifying ac4C are gaining increasing attention due to their cost-effectiveness, requiring minimal human and material resources. In this study, we propose an efficient and accurate computational framework, Caps-ac4C, for the precise detection of ac4C in human mRNA. Caps-ac4C utilizes chaos game representation to encode RNA sequences into "images" and employs capsule networks to learn global and local features from these RNA "images". Experimental results demonstrate that Caps-ac4C achieves state-of-the-art performance, achieving 95.47% accuracy and 0.912 MCC on the test set, surpassing the current best methods by 10.69% accuracy and 0.216 MCC. In summary, Caps-ac4C represents the most accurate tool for predicting ac4C sites in human mRNA, highlighting its significant contribution to RNA modification research. For user convenience, we developed a user-friendly web server, which can be accessed for free at:https://awi.cuhk.edu.cn/~Caps-ac4C/index.php.

摘要

N4-乙酰胞苷(ac4C)是人类mRNA中一种关键的转录后修饰,涉及胞苷第四位氮原子的乙酰化。这种修饰由N-乙酰转移酶(如NAT10)催化,主要存在于mRNA的编码区,可提高翻译效率和mRNA稳定性。ac4C与包括癌症在内的多种疾病密切相关。因此,准确识别人类mRNA中的ac4C对于深入了解疾病发病机制至关重要,并为新型医学干预措施的开发提供了潜在途径。由于其成本效益高,所需人力和物力资源最少,用于识别ac4C的计算机模拟方法越来越受到关注。在本研究中,我们提出了一种高效准确的计算框架Caps-ac4C,用于精确检测人类mRNA中的ac4C。Caps-ac4C利用混沌博弈表示将RNA序列编码为“图像”,并采用胶囊网络从这些RNA“图像”中学习全局和局部特征。实验结果表明,Caps-ac4C达到了目前的最佳性能,在测试集上的准确率为95.47%,马修斯相关系数(MCC)为0.912,准确率比当前最佳方法高出10.69%,MCC高出0.216。总之,Caps-ac4C是预测人类mRNA中ac4C位点最准确的工具,突出了其对RNA修饰研究的重大贡献。为方便用户,我们开发了一个用户友好的网络服务器,可通过以下网址免费访问:https://awi.cuhk.edu.cn/~Caps-ac4C/index.php

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