Improving drug response prediction via integrating gene relationships with deep learning

Predicting the drug response of cancer cell lines is crucial for advancing personalized cancer treatment, yet remains challenging due to tumor heterogeneity and individual diversity. In this study, we present a deep learning-based framework named Deep neural network Integrating Prior Knowledge (DIPK) (DIPK), which adopts self-supervised techniques to integrate multiple valuable information, including gene interaction relationships, gene expression profiles and molecular topologies, to enhance prediction accuracy and robustness. We demonstrated the superior performance of DIPK compared to existing methods on both known and novel cells and drugs, underscoring the importance of gene interaction relationships in drug response prediction. In addition, DIPK extends its applicability to single-cell RNA sequencing data, showcasing its capability for single-cell-level response prediction and cell identification. Further, we assess the applicability of DIPK on clinical data. DIPK accurately predicted a higher response to paclitaxel in the pathological complete response (pCR) group compared to the residual disease group, affirming the better response of the pCR group to the chemotherapy compound. We believe that the integration of DIPK into clinical decision-making processes has the potential to enhance individualized treatment strategies for cancer patients. Graphical Abstract