School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China.
Int J Mol Sci. 2023 Sep 15;24(18):14142. doi: 10.3390/ijms241814142.
Accurate identification of potential drug-target interactions (DTIs) is a crucial task in drug development and repositioning. Despite the remarkable progress achieved in recent years, improving the performance of DTI prediction still presents significant challenges. In this study, we propose a novel end-to-end deep learning model called AMMVF-DTI (attention mechanism and multi-view fusion), which leverages a multi-head self-attention mechanism to explore varying degrees of interaction between drugs and target proteins. More importantly, AMMVF-DTI extracts interactive features between drugs and proteins from both node-level and graph-level embeddings, enabling a more effective modeling of DTIs. This advantage is generally lacking in existing DTI prediction models. Consequently, when compared to many of the start-of-the-art methods, AMMVF-DTI demonstrated excellent performance on the human, , and DrugBank baseline datasets, which can be attributed to its ability to incorporate interactive information and mine features from both local and global structures. The results from additional ablation experiments also confirmed the importance of each module in our AMMVF-DTI model. Finally, a case study is presented utilizing our model for COVID-19-related DTI prediction. We believe the AMMVF-DTI model can not only achieve reasonable accuracy in DTI prediction, but also provide insights into the understanding of potential interactions between drugs and targets.
准确识别潜在的药物-靶标相互作用(DTIs)是药物开发和重新定位的关键任务。尽管近年来取得了显著的进展,但提高 DTI 预测的性能仍然存在重大挑战。在这项研究中,我们提出了一种名为 AMMVF-DTI(注意力机制和多视图融合)的新型端到端深度学习模型,该模型利用多头自注意力机制来探索药物和靶蛋白之间不同程度的相互作用。更重要的是,AMMVF-DTI 从节点级和图级嵌入中提取药物和蛋白质之间的交互特征,从而更有效地对 DTI 进行建模。这一优势在现有的 DTI 预测模型中通常是缺乏的。因此,与许多最先进的方法相比,AMMVF-DTI 在人类、 和 DrugBank 基准数据集上表现出了优异的性能,这归因于它能够整合交互信息并从局部和全局结构中挖掘特征。此外,消融实验的结果也证实了我们的 AMMVF-DTI 模型中每个模块的重要性。最后,我们提出了一个利用我们的模型进行 COVID-19 相关 DTI 预测的案例研究。我们相信,AMMVF-DTI 模型不仅可以在 DTI 预测中达到合理的准确性,还可以为理解药物和靶标之间的潜在相互作用提供深入的见解。
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