论文标题

层次图表示学习,用于预测药物 - 目标结合亲和力

Hierarchical Graph Representation Learning for the Prediction of Drug-Target Binding Affinity

论文作者

Chu, Zhaoyang, Liu, Shichao, Zhang, Wen

论文摘要

由于比二元相互作用预测更具体的解释,因此在药物发现过程中,药物靶标结合亲和力(DTA)的鉴定引起了人们的关注。最近,已经提出了许多基于深度学习的计算方法,以预测药物和目标之间受益于其令人满意的性能的结合亲和力。但是,先前的作品主要集中于编码药物和靶标的生物学特征和化学结构,而缺乏从药物目标亲和力网络中利用基本拓扑信息。在本文中,我们提出了一个新型的层次图表示模型,用于药物靶向结合亲和力预测,即HGRL-DTA。我们的模型的主要贡献是建立一个分层图学习结构,以结合药物/靶标分子的内在特性和药物目标对的拓扑亲和力。在此体系结构中,我们采用了一种消息广播机制来整合从全球级别亲和力图和局部级分子图中学到的层次结构表示。此外,我们设计了一个基于相似性的嵌入图,以解决推断看不见的药物和靶标表示的冷启动问题。在不同情况下,全面的实验结果表明,HGRL-DTA显着超过了最先进的模型,并显示了所有情况之间更好的模型概括。

The identification of drug-target binding affinity (DTA) has attracted increasing attention in the drug discovery process due to the more specific interpretation than binary interaction prediction. Recently, numerous deep learning-based computational methods have been proposed to predict the binding affinities between drugs and targets benefiting from their satisfactory performance. However, the previous works mainly focus on encoding biological features and chemical structures of drugs and targets, with a lack of exploiting the essential topological information from the drug-target affinity network. In this paper, we propose a novel hierarchical graph representation learning model for the drug-target binding affinity prediction, namely HGRL-DTA. The main contribution of our model is to establish a hierarchical graph learning architecture to incorporate the intrinsic properties of drug/target molecules and the topological affinities of drug-target pairs. In this architecture, we adopt a message broadcasting mechanism to integrate the hierarchical representations learned from the global-level affinity graph and the local-level molecular graph. Besides, we design a similarity-based embedding map to solve the cold start problem of inferring representations for unseen drugs and targets. Comprehensive experimental results under different scenarios indicate that HGRL-DTA significantly outperforms the state-of-the-art models and shows better model generalization among all the scenarios.

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