Wei Yuxiao, Tan Zhebin, Liu Liwei
College of Software, Dalian Jiaotong University, Dalian, 116028, China.
College of Science, Dalian Jiaotong University, Dalian, 116028, China.
Interdiscip Sci. 2025 Mar 27. doi: 10.1007/s12539-025-00694-7.
circRNAs are a type of single-stranded non-coding RNA molecules, and their unique feature is their closed circular structure. The interaction between circRNAs and RNA-binding proteins (RBPs) plays a key role in biological functions and is crucial for studying post-transcriptional regulatory mechanisms. The genome-wide circRNA binding event data obtained by cross-linking immunoprecipitation sequencing technology provides a foundation for constructing efficient computational model prediction methods. However, in existing studies, although machine learning techniques have been applied to predict circRNA-RBP interaction sites, these methods still have room for improvement in accuracy and lack interpretability. We propose CR-deal, which is an interpretable joint deep learning network that predicts the binding sites of circRNA and RBP through genome-wide circRNA data. CR-deal utilizes a graph attention network to unify sequence and structural features into the same view, more effectively utilizing structural features to improve accuracy. It can infer marker genes in the binding site through integrated gradient feature interpretation, thereby inferring functional structural regions in the binding site. We conducted benchmark tests on CR-deal on 37 circRNA datasets and 7 lncRNA datasets, respectively, and obtained the interpretability of CR-deal and discovered functional structural regions through 5 circRNA datasets. We believe that CR-deal can help researchers gain a deeper understanding of the functions and mechanisms of circRNA in living organisms and its critical role in the occurrence and development of diseases. The source code of CR-deal is provided free of charge on https://github.com/liuliwei1980/CR .
环状RNA(circRNAs)是一类单链非编码RNA分子,其独特特征是具有封闭的环状结构。circRNAs与RNA结合蛋白(RBPs)之间的相互作用在生物学功能中起关键作用,对于研究转录后调控机制至关重要。通过交联免疫沉淀测序技术获得的全基因组circRNA结合事件数据为构建高效的计算模型预测方法提供了基础。然而,在现有研究中,尽管机器学习技术已被应用于预测circRNA-RBP相互作用位点,但这些方法在准确性方面仍有提升空间,并且缺乏可解释性。我们提出了CR-deal,这是一种可解释的联合深度学习网络,通过全基因组circRNA数据预测circRNA与RBP的结合位点。CR-deal利用图注意力网络将序列和结构特征统一到同一视角,更有效地利用结构特征来提高准确性。它可以通过集成梯度特征解释推断结合位点中的标记基因,从而推断结合位点中的功能结构区域。我们分别在37个circRNA数据集和7个lncRNA数据集上对CR-deal进行了基准测试,并通过5个circRNA数据集获得了CR-deal的可解释性并发现了功能结构区域。我们相信CR-deal可以帮助研究人员更深入地了解circRNA在生物体中的功能和机制及其在疾病发生和发展中的关键作用。CR-deal的源代码可在https://github.com/liuliwei1980/CR上免费获取。