Feng Yihan, Yang Xixin, Guan Yuanlin, Zhang Jinyao, Yang Hang, Wang Zhongyu, Cheng Qi
College of Computer Science and Technology, Qingdao University, Qingdao, Shandong, China.
School of Automation, Qingdao University, Qingdao, Shandong, China.
PLoS One. 2025 Sep 9;20(9):e0331037. doi: 10.1371/journal.pone.0331037. eCollection 2025.
Drug-target interaction (DTI) prediction is essential for the development of novel drugs and the repurposing of existing ones. However, when the features of drug and target are applied to biological networks, there is a lack of capturing the relational features of drug-target interactions. And the corresponding multimodal models mainly depend on shallow fusion strategies, which results in suboptimal performance when trying to capture complex interaction relationships. Therefore, this study proposes a novel framework named KG-MACNF. This framework utilizes knowledge graph embedding (KGE) techniques to capture multi-level relational features of entities in large-scale biological networks. Simultaneously, our innovative PoolGAT network, along with CTD descriptors, is employed to extract drug structural features and protein sequence information. Finally, by employing our innovative nonlinear-driven cross-modal attention fusion network, the framework efficiently integrates these multimodal data and generates the final DTI prediction results. Experiments on two publicly available datasets, Yamanishi_08's and BioKG, demonstrate the substantial advantages of KG-MACNF in DTI prediction. KG-MACNF demonstrates robust stability, especially under imbalanced data conditions. This study successfully overcomes the bottlenecks of prior models in utilizing modality information and feature complementarity, providing a more accurate tool for drug discovery and DTI prediction.
药物-靶点相互作用(DTI)预测对于新型药物的研发和现有药物的重新利用至关重要。然而,当将药物和靶点的特征应用于生物网络时,缺乏对药物-靶点相互作用关系特征的捕捉。并且相应的多模态模型主要依赖于浅层融合策略,这在试图捕捉复杂相互作用关系时导致性能次优。因此,本研究提出了一种名为KG-MACNF的新型框架。该框架利用知识图谱嵌入(KGE)技术来捕捉大规模生物网络中实体的多层次关系特征。同时,我们创新的PoolGAT网络与CTD描述符一起用于提取药物结构特征和蛋白质序列信息。最后,通过采用我们创新的非线性驱动跨模态注意力融合网络,该框架有效地整合了这些多模态数据并生成最终的DTI预测结果。在两个公开可用数据集Yamanishi_08和BioKG上进行的实验证明了KG-MACNF在DTI预测方面的显著优势。KG-MACNF表现出强大的稳定性,尤其是在数据不平衡的情况下。本研究成功克服了先前模型在利用模态信息和特征互补性方面的瓶颈,为药物发现和DTI预测提供了更准确的工具。