A multi-task graph deep learning model to predict drugs combination of synergy and sensitivity scores.

Abstract

Background: Drug combination treatments have proven to be a realistic technique for treating challenging diseases such as cancer by enhancing efficacy and mitigating side effects. To achieve the therapeutic goals of these combinations, it is essential to employ multi-targeted drug combinations, which maximize effectiveness and synergistic effects.

Results: This paper proposes 'MultiComb', a multi-task deep learning (MTDL) model designed to simultaneously predict the synergy and sensitivity of drug combinations. The model utilizes a graph convolution network to represent the Simplified Molecular-Input Line-Entry (SMILES) of two drugs, generating their respective features. Also, three fully connected subnetworks extract features of the cancer cell line. These drug and cell line features are then concatenated and processed through an attention mechanism, which outputs two optimized feature representations for the target tasks. The cross-stitch model learns the relationship between these tasks. At last, each learned task feature is fed into fully connected subnetworks to predict the synergy and sensitivity scores. The proposed model is validated using the O'Neil benchmark dataset, which includes 38 unique drugs combined to form 17,901 drug combination pairs and tested across 37 unique cancer cells. The model's performance is tested using some metrics like mean square error ( $\mathrm{MSE}$ ), mean absolute error ( $\mathrm{MAE}$ ), coefficient of determination ( $R^2$ ), Spearman, and Pearson scores. The mean synergy scores of the proposed model are 232.37, 9.59, 0.57, 0.76, and 0.73 for the previous metrics, respectively. Also, the values for mean sensitivity scores are 15.59, 2.74, 0.90, 0.95, and 0.95, respectively.

Conclusion: This paper proposes an MTDL model to predict synergy and sensitivity scores for drug combinations targeting specific cancer cell lines. The MTDL model demonstrates superior performance compared to existing approaches, providing better results.