Wang Xin-Fei, Huang Lan, Wang Yan, Guan Ren-Chu, You Zhu-Hong, Zhou Feng-Feng, Li Yu-Qing, Zhao Zi-Qi
Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun 130012, China.
School of Computer Science, Northwestern Polytechnical University, Xi'an 710072, China.
J Chem Inf Model. 2025 Jun 23;65(12):6417-6430. doi: 10.1021/acs.jcim.5c01164. Epub 2025 Jun 12.
Competitive endogenous RNA (ceRNA) regulatory networks (CENA) have advanced our understanding of noncoding RNAs' roles in complex diseases, providing a theoretical basis for disease mechanisms. Existing ceRNA-disease association prediction methods are limited by traditional graph structures' inability to model long-range dependencies in biological networks. While hypergraph models partially address this, they often fail to effectively handle graph-level and node-level noise, hindering improvements in predictive performance. To address these challenges, we propose a Noise-Consistent hypeRgraph AutoEncoder framework with denoising strategies, termed NCRAE, aimed at achieving robust node embeddings in ceRNA regulatory networks and enabling the precise prediction of cancer-related ceRNA biomarkers. NCRAE employs a multiview contrastive learning strategy, integrating graph-level and node-level corruption with clean feature references to significantly enhance the robustness of hypergraph feature learning. Furthermore, to mitigate potential biases introduced by contrastive learning, NCRAE incorporates a noise consistency loss constraint, dynamically adjusting the weights of each component to further optimize the model's noise resistance and generalization ability. Combined with hypergraph convolution and Fourier KAN techniques, NCRAE achieves effective node embedding learning. Experiments on cancer-related ceRNA data sets show that NCRAE outperforms existing methods, especially in noisy conditions, demonstrating its robustness and predictive capability. Case studies further illustrate its practical value in cancer biomarker prediction, providing a powerful tool for cancer biomarker discovery.
竞争性内源RNA(ceRNA)调控网络(CENA)加深了我们对非编码RNA在复杂疾病中作用的理解,为疾病机制提供了理论基础。现有的ceRNA-疾病关联预测方法受到传统图结构无法对生物网络中的长程依赖性进行建模的限制。虽然超图模型部分解决了这一问题,但它们往往无法有效处理图级和节点级噪声,阻碍了预测性能的提升。为应对这些挑战,我们提出了一种带有去噪策略的噪声一致超图自动编码器框架,称为NCRAE,旨在在ceRNA调控网络中实现稳健的节点嵌入,并能够精确预测癌症相关的ceRNA生物标志物。NCRAE采用多视图对比学习策略,将图级和节点级损坏与干净的特征参考相结合,以显著增强超图特征学习的稳健性。此外,为减轻对比学习引入的潜在偏差,NCRAE纳入了噪声一致性损失约束,动态调整每个组件的权重,以进一步优化模型的抗噪声能力和泛化能力。结合超图卷积和傅里叶KAN技术,NCRAE实现了有效的节点嵌入学习。在癌症相关ceRNA数据集上的实验表明,NCRAE优于现有方法,尤其是在有噪声的条件下,证明了其稳健性和预测能力。案例研究进一步说明了其在癌症生物标志物预测中的实用价值,为癌症生物标志物发现提供了一个强大的工具。