Huang Shuhan, Wang Minhui, Zheng Xiao, Chen Jiajia, Tang Chang
IEEE J Biomed Health Inform. 2024 Feb 6;PP. doi: 10.1109/JBHI.2024.3363080.
In the realm of biomedicine, the prediction of associations between drugs and diseases holds significant importance. Yet, conventional wet lab experiments often fall short of meeting the stringent demands for prediction accuracy and efficiency. Many prior studies have predominantly focused on drug and disease similarities to predict drug-disease associations, but overlooking the crucial interactions between drugs and diseases that are essential for enhancing prediction accuracy. Hence, in this paper, a resilient and effective model named Hierarchical and Dynamic Graph Attention Network (HDGAT) has been proposed to predict drug-disease associations. Firstly, it establishes a heterogeneous graph by leveraging the interplay of drug and disease similarities and associations. Subsequently, it harnesses the capabilities of graph convolutional networks and bidirectional long short-term memory networks (Bi-LSTM) to aggregate node-level information within the heterogeneous graph comprehensively. Furthermore, it incorporates a hierarchical attention mechanism between convolutional layers and a dynamic attention mechanism between nodes to learn embeddings for drugs and diseases. The hierarchical attention mechanism assigns varying weights to embeddings learned from different convolutional layers, and the dynamic attention mechanism efficiently prioritizes inter-node information by allocating each node with varying rankings of attention coefficients for neighbour nodes. Moreover, it employs residual connections to alleviate the over-smoothing issue in graph convolution operations. The latent drug-disease associations are quantified through the fusion of these embeddings ultimately. By conducting 5-fold cross-validation, HDGAT's performance surpasses the performance of existing state-of-the-art models across various evaluation metrics, which substantiates the exceptional efficacy of HDGAT in predicting drug-disease associations.
在生物医学领域,预测药物与疾病之间的关联具有重要意义。然而,传统的湿实验室实验往往难以满足对预测准确性和效率的严格要求。许多先前的研究主要集中在药物和疾病的相似性上,以预测药物-疾病关联,但忽略了药物与疾病之间的关键相互作用,而这些相互作用对于提高预测准确性至关重要。因此,本文提出了一种名为分层动态图注意力网络(HDGAT)的弹性且有效的模型来预测药物-疾病关联。首先,它通过利用药物和疾病的相似性与关联的相互作用建立了一个异构图。随后,它利用图卷积网络和双向长短期记忆网络(Bi-LSTM)的能力,全面聚合异构图内的节点级信息。此外,它在卷积层之间引入了分层注意力机制,在节点之间引入了动态注意力机制,以学习药物和疾病的嵌入。分层注意力机制为从不同卷积层学习到的嵌入分配不同的权重,动态注意力机制通过为每个节点分配不同的邻居节点注意力系数排名,有效地对节点间信息进行优先级排序。此外,它采用残差连接来缓解图卷积操作中的过平滑问题。最终,通过融合这些嵌入来量化潜在的药物-疾病关联。通过进行5折交叉验证,HDGAT在各种评估指标上的性能超过了现有最先进模型的性能,这证实了HDGAT在预测药物-疾病关联方面的卓越功效。