Predicting Drug-Target Affinity by Learning Protein Knowledge From Biological Networks.

Predicting drug-target affinity (DTA) is a crucial step in the process of drug discovery. Efficient and accurate prediction of DTA would greatly reduce the time and economic cost of new drug development, which has encouraged the emergence of a large number of deep learning-based DTA prediction methods. In terms of the representation of target proteins, current methods can be classified into 1D sequence- and 2D-protein graph-based methods. However, both two approaches focused only on the inherent properties of the target protein, but neglected the broad prior knowledge regarding protein interactions that have been clearly elucidated in past decades. Aiming at the above issue, this work presents an end-to-end DTA prediction method named MSF-DTA (Multi-Source Feature Fusion-based Drug-Target Affinity). The contributions can be summarized as follows. First, MSF-DTA adopts a novel "neighboring feature"-based protein representation. Instead of utilizing only the inherent features of a target protein, MSF-DTA gathers additional information for the target protein from its biologically related "neighboring" proteins in PPI (i.e., protein-protein interaction) and SSN (i.e., sequence similarity) networks to get prior knowledge. Second, the representation was learned using an advanced graph pre-training framework, VGAE, which could not only gather node features but also learn topological connections, therefore contributing to a richer protein representation and benefiting the downstream DTA prediction task. This study provides new perspective for the DTA prediction task, and evaluation results demonstrated that MSF-DTA obtained superior performances compared to current state-of-the-art methods.