DeepTTA: a transformer-based model for predicting cancer drug response.

Abstract

Identifying new lead molecules to treat cancer requires more than a decade of dedicated effort. Before selected drug candidates are used in the clinic, their anti-cancer activity is generally validated by in vitro cellular experiments. Therefore, accurate prediction of cancer drug response is a critical and challenging task for anti-cancer drugs design and precision medicine. With the development of pharmacogenomics, the combination of efficient drug feature extraction methods and omics data has made it possible to use computational models to assist in drug response prediction. In this study, we propose DeepTTA, a novel end-to-end deep learning model that utilizes transformer for drug representation learning and a multilayer neural network for transcriptomic data prediction of the anti-cancer drug responses. Specifically, DeepTTA uses transcriptomic gene expression data and chemical substructures of drugs for drug response prediction. Compared to existing methods, DeepTTA achieved higher performance in terms of root mean square error, Pearson correlation coefficient and Spearman's rank correlation coefficient on multiple test sets. Moreover, we discovered that anti-cancer drugs bortezomib and dactinomycin provide a potential therapeutic option with multiple clinical indications. With its excellent performance, DeepTTA is expected to be an effective method in cancer drug design.