HiSIF-DTA: A Hierarchical Semantic Information Fusion Framework for Drug-Target Affinity Prediction.

Abstract

Accurately identifying drug-target affinity (DTA) plays a significant role in promoting drug discovery and has attracted increasing attention in recent years. Exploring appropriate protein representation methods and increasing the abundance of protein information is critical in enhancing the accuracy of DTA prediction. Recently, numerous deep learning-based models have been proposed to utilize the sequential or structural features of target proteins. However, these models capture only the low-order semantics that exist in a single protein, while the high-order semantics abundant in biological networks are largely ignored. In this article, we propose HiSIF-DTA'a hierarchical semantic information fusion framework for DTA prediction. In this framework, a hierarchical protein graph is constructed that includes not only contact maps as low-order structural semantics but also protein-rotein interaction (PPI) networks as high-order functional semantics. Particularly, two distinct hierarchical fusion strategies (i.e., Top-down and Bottom-Up) are designed to integrate the different protein semantics, therefore contributing to a richer protein representation. Comprehensive experimental results demonstrate that HiSIF-DTA outperforms current state-of-the-art methods for prediction on the benchmark datasets of the DTA task. Further validation on binary tasks and visualization analysis demonstrates the generalization and interpretation abilities of the proposed method.