Drug combination therapy has exhibited remarkable therapeutic efficacy and has gradually become a promising clinical treatment strategy of complex diseases such as cancers. As the related databases keep expanding, computational methods based on deep learning model have become powerful tools to predict synergistic drug combinations. However, predicting effective synergistic drug combinations is still a challenge due to the high complexity of drug combinations, the lack of biological interpretability, and the large discrepancy in the response of drug combinations in vivo and in vitro biological systems.


Here, we propose DGSSynADR, a new deep learning method based on global structured features of drugs and targets for predicting synergistic anticancer drug combinations. DGSSynADR constructs a heterogeneous graph by integrating the drug–drug, drug–target, protein–protein interactions and multi-omics data, utilizes a low-rank global attention (LRGA) model to perform global weighted aggregation of graph nodes and learn the global structured features of drugs and targets, and then feeds the embedded features into a bilinear predictor to predict the synergy scores of drug combinations in different cancer cell lines. Specifically, LRGA network brings better model generalization ability, and effectively reduces the complexity of graph computation. The bilinear predictor facilitates the dimension transformation of the features and fuses the feature representation of the two drugs to improve the prediction performance. The loss function Smooth L1 effectively avoids gradient explosion, contributing to better model convergence. To validate the performance of DGSSynADR, we compare it with seven competitive methods. The comparison results demonstrate that DGSSynADR achieves better performance. Meanwhile, the prediction of DGSSynADR is validated by previous findings in case studies. Furthermore, detailed ablation studies indicate that the one-hot coding drug feature, LRGA model and bilinear predictor play a key role in improving the prediction performance.

Availability and implementation

DGSSynADR is implemented in Python using the Pytorch machine-learning library, and it is freely available at

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