Li Guodong, Su Xiaorui, Yang Yue, Li Dongxu, Cui Ziwen, Deng Xun, Hu Pengwei, Hu Lun
Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi, China.
University of Chinese Academy of Sciences, Beijing, China.
Commun Biol. 2025 Jul 8;8(1):1022. doi: 10.1038/s42003-025-08265-8.
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.
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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