基于半监督异质图对比学习的药物-靶标相互作用预测。

Semi-supervised heterogeneous graph contrastive learning for drug-target interaction prediction.

机构信息

School of Software Engineering, Tongji University, 4800 Caoan Road, Jiading District, Shanghai, 201804, China.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University), Ministry of Education, Orthopaedic Department of Tongji Hospital, Bioinformatics Department, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Yangpu District, Shanghai, 200092, China.

出版信息

Comput Biol Med. 2023 Sep;163:107199. doi: 10.1016/j.compbiomed.2023.107199. Epub 2023 Jun 22.

Abstract

Identification of drug-target interactions (DTIs) is an important step in drug discovery and drug repositioning. In recent years, graph-based methods have attracted great attention and show advantages on predicting potential DTIs. However, these methods face the problem that the known DTIs are very limited and expensive to obtain, which decreases the generalization ability of the methods. Self-supervised contrastive learning is independent of labeled DTIs, which can mitigate the impact of the problem. Therefore, we propose a framework SHGCL-DTI for predicting DTIs, which supplements the classical semi-supervised DTI prediction task with an auxiliary graph contrastive learning module. Specifically, we generate representations for the nodes through the neighbor view and meta-path view, and define positive and negative pairs to maximize the similarity between positive pairs from different views. Subsequently, SHGCL-DTI reconstructs the original heterogeneous network to predict the potential DTIs. The experiments on the public dataset show that SHGCL-DTI has significant improvement in different scenarios, compared with existing state-of-the-art methods. We also demonstrate that the contrastive learning module improves the prediction performance and generalization ability of SHGCL-DTI through ablation study. In addition, we have found several novel predicted DTIs supported by the biological literature. The data and source code are available at: https://github.com/TOJSSE-iData/SHGCL-DTI.

摘要

鉴定药物-靶点相互作用(DTIs)是药物发现和药物重定位的重要步骤。近年来,基于图的方法引起了极大的关注,并在预测潜在 DTIs 方面显示出优势。然而,这些方法面临着一个问题,即已知的 DTIs 非常有限,并且获取成本很高,这降低了方法的泛化能力。自监督对比学习独立于标记的 DTIs,可以减轻这个问题的影响。因此,我们提出了一个用于预测 DTIs 的框架 SHGCL-DTI,该框架用一个辅助图对比学习模块补充了经典的半监督 DTI 预测任务。具体来说,我们通过邻居视图和元路径视图为节点生成表示,并定义正例和负例,以最大化来自不同视图的正例之间的相似度。随后,SHGCL-DTI 重构原始的异构网络以预测潜在的 DTIs。在公共数据集上的实验表明,与现有最先进的方法相比,SHGCL-DTI 在不同场景下都有显著的改进。通过消融研究,我们还证明了对比学习模块提高了 SHGCL-DTI 的预测性能和泛化能力。此外,我们还发现了一些基于生物文献支持的新的预测 DTIs。数据和源代码可在:https://github.com/TOJSSE-iData/SHGCL-DTI 获得。

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