Graph Neural Network and BERT Model for Antimalarial Drug Predictions Using Plasmodium Potential Targets

Malaria continues to pose a significant global health burden despite concerted efforts to combat it. In 2020, nearly half of the world’s population faced the risk of malaria, underscoring the urgency of innovative strategies to tackle this pervasive threat. One of the major challenges lies in the emergence of the resistance of parasites to existing antimalarial drugs. This challenge necessitates the discovery of new, effective treatments capable of combating the Plasmodium parasite at various stages of its life cycle. Advanced computational approaches have been utilized to accelerate drug development, playing a crucial role in every stage of the drug discovery and development process. We have witnessed impressive and groundbreaking achievements, with GNNs applied to graph data and BERT from transformers across diverse NLP text analysis tasks. In this study, to facilitate a more efficient and effective approach, we proposed the integration of an NLP based model for SMILES (i.e., BERT) and a GNN model (i.e., RGCN) to predict the effect of antimalarial drugs against Plasmodium. The GNN model was trained using designed antimalarial drug and potential target (i.e., PfAcAS, F/GGPPS, and PfMAGL) graph-structured data with nodes representing antimalarial drugs and potential targets, and edges representing relationships between them. The performance of BERT-RGCN was further compared with that of Mordred-RGCN to evaluate its effectiveness. The BERT-RGCN and Mordred-RGCN models performed consistently well across different feature combinations, showcasing high accuracy, sensitivity, specificity, MCC, AUROC, and AUPRC values. These results suggest the effectiveness of the models in predicting antimalarial drugs against Plasmodium falciparum in various scenarios based on different sets of features of drugs and potential antimalarial targets.