A multi-task learning model for predicting drugs combination synergy by analyzing drug–drug interactions and integrated multi-view graph data

Abstract

Abstract This paper proposes a multi-task deep learning model for determining drug combination synergistic by simultaneously output synergy scores and synergy class labels. Initially, the two drugs are represented using a Simplified Molecular-Input Line-Entry (SMILE) system. Chemical structural features of the drugs are extracted from the SMILE using the RedKit package. Additionally, an improved Multi-view representation is proposed to extract graph-based drug features. Furthermore, the cancer cell line is represented by gene expression. Then, a three fully connected layers are learned to extract cancer cell line features. To investigate the impact of drug interactions on cell lines, the drug interaction features are extracted from a pretrained drugs interaction network and fed into an attention mechanism along with the cancer cell line features, resulting in the output of affected cancer cell line features. Subsequently, the drug and cell line features are concatenated and fed into an attention mechanism, which produces a two-feature representation for the two predicted tasks. The relationship between the two tasks is learned using the cross-stitch algorithm. Finally, each task feature is inputted into a fully connected subnetwork to predict the synergy score and synergy label. The proposed model ‘MutliSyn’ is evaluated using the O'Neil cancer dataset, comprising 38 unique drugs combined to form 22,737 drug combination pairs, tested on 39 cancer cell lines. For the synergy score, the model achieves a mean square error (MSE) of 219.14, a root mean square error (RMSE) of 14.75, and a Pearson score of 0.76. Regarding the synergy class label, the model achieves an area under the ROC curve (ROC-AUC) of 0.95, an area under the precision-recall curve (PR-AUC) of 0.85, precision of 0.93, kappa of 0.61, and accuracy of 0.90.