A multi-view feature representation for predicting drugs combination synergy based on ensemble and multi-task attention models

Abstract

Abstract This paper proposes a novel multi-view ensemble predictor model that is designed to address the challenge of determining synergistic drug combinations by predicting both the synergy score value values and synergy class label of drug combinations with cancer cell lines. The proposed methodology involves representing drug features through four distinct views: Simplified Molecular-Input Line-Entry System (SMILES) features, molecular graph features, fingerprint features, and drug-target features. On the other hand, cell line features are captured through four views: gene expression features, copy number features, mutation features, and proteomics features. To prevent overfitting of the model, two techniques are employed. First, each view feature of a drug is paired with each corresponding cell line view and input into a multi-task attention deep learning model. This multi-task model is trained to simultaneously predict both the synergy score value and synergy class label. This process results in sixteen input view features being fed into the multi-task model, producing sixteen prediction values. Subsequently, these prediction values are utilized as inputs for an ensemble model, which outputs the final prediction value. The ‘MVME’ model is assessed using the O’Neil dataset, which includes 38 distinct drugs combined across 39 distinct cancer cell lines to output 22,737 drug combination pairs. For the synergy score value, the proposed model scores a mean square error (MSE) of 206.57, a root mean square error (RMSE) of 14.30, and a Pearson score of 0.76. For the synergy class label, the model scores 0.90 for accuracy, 0.96 for precision, 0.57 for kappa, 0.96 for the area under the ROC curve (ROC-AUC), and 0.88 for the area under the precision-recall curve (PR-AUC).

Keywords

• Multi-task
• Attention
• Multi-view features
• Copy number
• Proteomics
• Gene expression