Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, 430070, China.
Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, 518000, China.
BMC Bioinformatics. 2023 Jan 17;24(1):18. doi: 10.1186/s12859-022-05073-3.
Emerging evidences show that Piwi-interacting RNAs (piRNAs) play a pivotal role in numerous complex human diseases. Identifying potential piRNA-disease associations (PDAs) is crucial for understanding disease pathogenesis at molecular level. Compared to the biological wet experiments, the computational methods provide a cost-effective strategy. However, few computational methods have been developed so far.
Here, we proposed an end-to-end model, referred to as PDA-PRGCN (PDA prediction using subgraph Projection and Residual scaling-based feature augmentation through Graph Convolutional Network). Specifically, starting with the known piRNA-disease associations represented as a graph, we applied subgraph projection to construct piRNA-piRNA and disease-disease subgraphs for the first time, followed by a residual scaling-based feature augmentation algorithm for node initial representation. Then, we adopted graph convolutional network (GCN) to learn and identify potential PDAs as a link prediction task on the constructed heterogeneous graph. Comprehensive experiments, including the performance comparison of individual components in PDA-PRGCN, indicated the significant improvement of integrating subgraph projection, node feature augmentation and dual-loss mechanism into GCN for PDA prediction. Compared with state-of-the-art approaches, PDA-PRGCN gave more accurate and robust predictions. Finally, the case studies further corroborated that PDA-PRGCN can reliably detect PDAs.
PDA-PRGCN provides a powerful method for PDA prediction, which can also serve as a screening tool for studies of complex diseases.
新兴证据表明,Piwi 相互作用 RNA(piRNA)在许多复杂的人类疾病中发挥着关键作用。鉴定潜在的 piRNA-疾病关联(PDAs)对于在分子水平上理解疾病发病机制至关重要。与生物湿实验相比,计算方法提供了一种具有成本效益的策略。然而,到目前为止,开发的计算方法还很少。
在这里,我们提出了一个端到端模型,称为 PDA-PRGCN(使用子图投影和基于残差缩放的特征增强的 PDA 预测通过图卷积网络)。具体来说,从表示为图的已知 piRNA-疾病关联开始,我们首次应用子图投影来构建 piRNA-piRNA 和疾病-疾病子图,然后应用基于残差缩放的特征增强算法对节点初始表示进行处理。然后,我们采用图卷积网络(GCN)来学习和识别潜在的 PDAs,作为构建的异构图上的链接预测任务。包括 PDA-PRGCN 中各个组件的性能比较在内的综合实验表明,将子图投影、节点特征增强和双损失机制集成到 GCN 中对于 PDA 预测的显著改进。与最先进的方法相比,PDA-PRGCN 提供了更准确和稳健的预测。最后,案例研究进一步证实了 PDA-PRGCN 可以可靠地检测 PDAs。
PDA-PRGCN 为 PDA 预测提供了一种强大的方法,也可以作为复杂疾病研究的筛选工具。