HiDRA: Hierarchical Network for Drug Response Prediction with Attention.

Understanding differences in drug responses between patients is crucial for delivering effective cancer treatment. We describe an interpretable AI model for use in predicting drug responses in cancer cells at the gene, molecular pathway, and drug level, which we have called the hierarchical network for drug response prediction with attention. We found that the model shows better accuracy in predicting drugs having efficacy against a given cell line than other state-of-the-art methods, with a root mean squared error of 1.0064, a Pearson's correlation coefficient of 0.9307, and an R2 value of 0.8647. We also confirmed that the model gives high attention to drug-target genes and cancer-related pathways when predicting a response. The validity of predicted results was proven by in vitro cytotoxicity assay. Overall, we propose that our hierarchical and interpretable AI-based model is capable of interpreting intrinsic characteristics of cancer cells and drugs for accurate prediction of cancer-drug responses.