Hierarchical graph representation learning with multi-granularity features for anti-cancer drug response prediction.

Patients with the same type of cancer often respond differently to identical drug treatments due to unique genomic traits. Accurately predicting a patient's response to drug is crucial in guiding treatment decisions, alleviating patient suffering, and improving cancer prognosis. Current computational methods utilize deep learning models trained on extensive drug screening data to predict anti-cancer drug responses based on features of cell lines and drugs. However, the interaction between cell lines and drugs is a complex biological process involving interactions across various levels, from internal cellular and drug structures to the external interactions among different molecules.To address this complexity, we propose a novel Hierarchical graph representation Learning with Multi-Granularity features (HLMG) algorithm for predicting anti-cancer drug responses. The HLMG algorithm combines features at two granularities: the overall gene expression and pathway substructures of cell lines, and the overall molecular fingerprints and substructures of drugs. Subsequently, it constructs a heterogeneous graph including cell lines, drugs, known cell line-drug responses, and the associations between similar cell lines and similar drugs. Through a graph convolutional network model, the HLMG learns the final cell line and drug representations by aggregating features of their multi-level neighbor in the heterogeneous graph. The multi-level neighbors consist of the node self, directly related drugs/cell lines, and indirectly related similar drugs/cell lines. Finally, a linear correlation coefficient decoder is employed to reconstruct the cell line-drug correlation matrix to predict anti-cancer drug responses. Our model was tested on the Genomics of Drug Sensitivity in Cancer (GDSC) and the Cancer Cell Line Encyclopedia (CCLE) databases. Results indicate that HLMG outperforms other state-of-the-art methods in accurately predicting anti-cancer drug responses.