GPDRP: a multimodal framework for drug response prediction with graph transformer

Abstract Background In the field of computational personalized medicine, drug response prediction (DRP) is a critical issue. However, existing studies often characterize drugs as strings, a representation that does not align with the natural description of molecules. Additionally, they ignore gene pathway-specific combinatorial implication. Results In this study, we propose drug Graph and gene Pathway based Drug response prediction method (GPDRP), a new multimodal deep learning model for predicting drug responses based on drug molecular graphs and gene pathway activity. In GPDRP, drugs are represented by molecular graphs, while cell lines are described by gene pathway activity scores. The model separately learns these two types of data using Graph Neural Networks (GNN) with Graph Transformers and deep neural networks. Predictions are subsequently made through fully connected layers. Conclusions Our results indicate that Graph Transformer-based model delivers superior performance. We apply GPDRP on hundreds of cancer cell lines’ bulk RNA-sequencing data, and it outperforms some recently published models. Furthermore, the generalizability and applicability of GPDRP are demonstrated through its predictions on unknown drug-cell line pairs and xenografts. This underscores the interpretability achieved by incorporating gene pathways.