几何增强型图神经网络加速环状RNA治疗靶点发现。
Geometry-enhanced graph neural networks accelerate circRNA therapeutic target discovery.
作者信息
Li Zhen, Qi Mingming, Huang Juyuan, Zhang Wei, Tan Xu, Chen Yifan
机构信息
School of Artificial Intelligence, Shenzhen Institute of Information Technology, Shenzhen, China.
School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, China.
出版信息
Front Genet. 2025 Jul 7;16:1633391. doi: 10.3389/fgene.2025.1633391. eCollection 2025.
Circular RNAs (circRNAs) play pivotal roles in various biological processes and disease progression, particularly in modulating drug responses and resistance mechanisms. Accurate prediction of circRNA-drug associations (CDAs) is essential for biomarker discovery and the advancement of therapeutic strategies. Although several computational approaches have been proposed for identifying novel circRNA therapeutic targets, their performance is often limited by inadequate modeling of higher-order geometric information within circRNA-drug interaction networks. To overcome these challenges, we propose G2CDA, a geometric graph representation learning framework specifically designed to enhance the identification of CDAs and facilitate therapeutic target discovery. G2CDA introduces torsion-based geometric encoding into the message propagation process of the circRNA-drug network. For each potential association, we construct local simplicial complexes, extract their geometric features, and integrate these features as adaptive weights during message propagation and aggregation. This design promotes a richer understanding of local topological structures, thereby improving the robustness and expressiveness of learned circRNA and drug representations. Extensive benchmark evaluations on public datasets demonstrate that G2CDA outperforms state-of-the-art CDA prediction models, particularly in identifying novel associations. Case studies further confirm its effectiveness by uncovering potential drug interactions with the ALDH3A2 and ANXA2 biomarkers. Collectively, G2CDA provides a robust and interpretable framework for accelerating circRNA-based therapeutic target discovery and streamlining drug development pipelines. Our code are archived in: https://github.com/lizhen5000/G2CDA.
环状RNA(circRNAs)在各种生物学过程和疾病进展中发挥着关键作用,特别是在调节药物反应和耐药机制方面。准确预测环状RNA与药物的关联(CDAs)对于生物标志物的发现和治疗策略的推进至关重要。尽管已经提出了几种计算方法来识别新的环状RNA治疗靶点,但其性能往往受到环状RNA-药物相互作用网络中高阶几何信息建模不足的限制。为了克服这些挑战,我们提出了G2CDA,这是一种几何图表示学习框架,专门设计用于增强CDAs的识别并促进治疗靶点的发现。G2CDA将基于扭转的几何编码引入到环状RNA-药物网络的消息传播过程中。对于每个潜在的关联,我们构建局部单纯复形,提取其几何特征,并在消息传播和聚合过程中将这些特征作为自适应权重进行整合。这种设计促进了对局部拓扑结构更丰富的理解,从而提高了所学习的环状RNA和药物表示的鲁棒性和表现力。在公共数据集上进行的广泛基准评估表明,G2CDA优于现有的CDA预测模型,特别是在识别新关联方面。案例研究通过揭示与ALDH3A2和ANXA2生物标志物的潜在药物相互作用进一步证实了其有效性。总体而言,G2CDA为加速基于环状RNA的治疗靶点发现和简化药物开发流程提供了一个强大且可解释的框架。我们的代码存档于:https://github.com/lizhen5000/G2CDA。
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