End-to-End Intelligent Drug Discovery via a Scalable and Explainable Graph-Transformer Framework

Abstract

Drug discovery is still an expensive and time-consuming process where finding the right drug associations is important for therapeutic development. In this paper, a new system is proposed for drug design called PharmaGraphFormer (PGF). It consists of five stages: (i) Data acquisition and preprocessing (DAP), (ii) Feature extraction and feature fusion (FEF), (iii) Molecular representation (MR), (iv) Multi-task prediction, and (v) Explainable artificial intelligence (XAI). This study employs a hybrid graph neural network (GNN)-transformer architecture that combines structural and sequence-based representations. Through DAP, several processes are executed, including the imputation or removal of missing values, outlier rejection, and class balancing. Next, through FEF1, features are extracted to represent the input data efficiently. Initially, compound-protein features are generated to document the interactions and relationships between chemical compounds and their corresponding target proteins. Secondly, drug characterizations are computed to encapsulate the physical, chemical, and structural attributes of each drug. After that, MR is performed using a graph-based molecule representation. Then, a novel model integrating GNNs and graph transformers, termed GNN-T, is proposed. Initially, GNNs represent the most promising deep learning models adept at processing non-Euclidean data. The Graph Transformer layer enhances atom representations by consolidating the representations of adjacent atoms through an attention mechanism. Finally, XAI is applied to explain the internal mechanisms of AI systems, rendering them comprehensible and interpretable. Across five independent runs, the proposed model achieved an accuracy of 0.963±0.002, a precision of 0.971±0.002, a recall of 0.958±0.003, an F1-score of 0.964±0.002, and a ROC-AUC of 0.993±0.001. These results demonstrate an outstanding performance when compared with all other models and emphasize that the proposed model is reliable in solving the problems of prioritizing compounds in line with the latest developments in AI-powered virtual screening and drug–target interaction modeling.