Zeng Sihao, Zhang Shanwen, Wang Zhen, Yang Chen, Yuan Shenao
School of Electronic Information, Xijing University, Xi'an 710123, China.
Genes (Basel). 2025 Apr 1;16(4):425. doi: 10.3390/genes16040425.
Small non-coding molecules known as microRNAs (miRNAs) play a critical role in disease diagnosis, treatment, and prognosis evaluation. Traditional wet-lab methods for validating miRNA-disease associations are often time-consuming and inefficient. With the advancement of high-throughput sequencing technologies, deep learning methods have become effective tools for uncovering potential patterns in miRNA-disease associations and revealing novel biological insights. Most of the existing approaches focus primarily on individual molecular behavior, overlooking interactions at the multi-molecular level. Conventional graph neural network (GNN) models struggle to generalize to heterogeneous graphs, and as network depth increases, node representations become indistinguishable due to over-smoothing, resulting in reduced predictive performance. GONNMDA first integrates similarity features from multiple data sources and applies noise reduction to obtain a reconstructed, comprehensive similarity representation. It then constructs heterogeneous graphs and applies a root-tree hierarchical alignment, along with an ordered gating message-passing mechanism, effectively addressing the challenges of heterogeneity and over-smoothing. Finally, a multilayer perceptron is employed to produce the final association predictions. To evaluate the effectiveness of GONNMDA, we conducted extensive experiments where the model achieved an AUC of 95.49% and an AUPR of 95.32%. The results demonstrate that GONNMDA outperforms several recent state-of-the-art methods. In addition, case studies and survival analyses on three common human cancers-breast cancer, rectal cancer, and lung cancer-further validate the effectiveness and reliability of GONNMDA in predicting miRNA-disease associations.
被称为微小RNA(miRNA)的小型非编码分子在疾病诊断、治疗和预后评估中发挥着关键作用。传统的用于验证miRNA与疾病关联的湿实验室方法通常耗时且效率低下。随着高通量测序技术的发展,深度学习方法已成为揭示miRNA与疾病关联中潜在模式并揭示新的生物学见解的有效工具。现有的大多数方法主要关注单个分子行为,而忽略了多分子水平的相互作用。传统的图神经网络(GNN)模型难以推广到异构图,并且随着网络深度的增加,由于过度平滑,节点表示变得难以区分,导致预测性能下降。GONNMDA首先整合来自多个数据源的相似性特征并进行降噪以获得重建的综合相似性表示。然后它构建异构图并应用根树层次对齐以及有序门控消息传递机制,有效解决了异质性和过度平滑的挑战。最后,使用多层感知器来产生最终的关联预测。为了评估GONNMDA的有效性,我们进行了广泛的实验,该模型的AUC达到95.49%,AUPR达到95.32%。结果表明,GONNMDA优于最近的几种先进方法。此外,对三种常见人类癌症——乳腺癌、直肠癌和肺癌——的案例研究和生存分析进一步验证了GONNMDA在预测miRNA与疾病关联方面的有效性和可靠性。