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基于可逆神经网络的可解释性引导的RNA N-甲基腺苷修饰位点预测

Interpretability-guided RNA N-methyladenosine modification site prediction with invertible neural networks.

作者信息

Li Guodong, Su Xiaorui, Yang Yue, Li Dongxu, Cui Ziwen, Deng Xun, Hu Pengwei, Hu Lun

机构信息

Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

Commun Biol. 2025 Jul 8;8(1):1022. doi: 10.1038/s42003-025-08265-8.


DOI:10.1038/s42003-025-08265-8
PMID:40629144
Abstract

As one of the most common and abundant post-transcriptional modifications, N-methyladenosine (mA) has been extensively studied for its essential regulatory role in gene expression and cell functions. The location of mA RNA modification sites, however, remains a challenging problem, because of the inability to characterize mA modified sites at a multi-scale level in their native RNA context. Here, we introduce an interpretability-guided invertible neural network (mA-IIN), a deep learning model to accurately identify mA RNA modification sites by integrating both primary and secondary structure information under an invertible coupling framework. Compared to existing methods, mA-IIN achieves state-of-the-art performance in the prediction of mA RNA modification sites across 11 benchmark datasets collected from different species and tissues. Furthermore, we find evidence indicating high consistency in methylation-related regions between primary and secondary structure of RNA, providing novel insights into mA biology from the phylogenetic perspective. By analyzing conserved methylation-related regions identified by mA-IIN across tissues, mA-IIN facilitates the identification of novel pan-cancer genes, providing valuable contributions to cancer biology. Our results underscore the interpretability and predictive accuracy of mA-IIN, opening an avenue towards the understanding of mA RNA modification mechanisms.

摘要

作为最常见且丰富的转录后修饰之一,N6-甲基腺苷(m6A)因其在基因表达和细胞功能中的重要调控作用而受到广泛研究。然而,由于无法在天然RNA环境中多尺度地表征m6A修饰位点,m6A RNA修饰位点的定位仍然是一个具有挑战性的问题。在此,我们引入了一种可解释性引导的可逆神经网络(m6A-IIN),这是一种深度学习模型,可通过在可逆耦合框架下整合一级和二级结构信息来准确识别m6A RNA修饰位点。与现有方法相比,m6A-IIN在预测来自不同物种和组织的11个基准数据集的m6A RNA修饰位点方面达到了当前的最佳性能。此外,我们发现有证据表明RNA的一级和二级结构之间在甲基化相关区域具有高度一致性,从系统发育角度为m6A生物学提供了新的见解。通过分析m6A-IIN在不同组织中鉴定出的保守甲基化相关区域,m6A-IIN有助于鉴定新的泛癌基因,为癌症生物学做出了有价值的贡献。我们的结果强调了m6A-IIN的可解释性和预测准确性,为理解m6A RNA修饰机制开辟了一条途径。

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Interpretability-guided RNA N-methyladenosine modification site prediction with invertible neural networks.

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本文引用的文献

[1]
Interpretable identification of cancer genes across biological networks via transformer-powered graph representation learning.

Nat Biomed Eng. 2025-3

[2]
OmicShare tools: A zero-code interactive online platform for biological data analysis and visualization.

Imeta. 2024-8-1

[3]
MA modification in cardiovascular disease: With a focus on programmed cell death.

Genes Dis. 2023-7-14

[4]
Transfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing.

Nat Commun. 2024-5-14

[5]
Insights into the role of RNA mA modification in the metabolic process and related diseases.

Genes Dis. 2023-7-4

[6]
A comprehensive analysis of the prognostic and immunological role of in pan-cancer.

Transl Cancer Res. 2024-2-29

[7]
Determinant of m6A regional preference by transcriptional dynamics.

Nucleic Acids Res. 2024-4-24

[8]
Alternative splicing and related RNA binding proteins in human health and disease.

Signal Transduct Target Ther. 2024-2-2

[9]
Discovering Consensus Regions for Interpretable Identification of RNA N6-Methyladenosine Modification Sites via Graph Contrastive Clustering.

IEEE J Biomed Health Inform. 2024-4

[10]
Interpretable prediction models for widespread m6A RNA modification across cell lines and tissues.

Bioinformatics. 2023-12-1

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