Deep Model for Anticancer Drug Response through Genomic Profiles and Compound Structures

Abstract

Cancer is among the deadliest diseases, enhancing the need for its detection and treatment. In the era of precision medicine, the main goal is to take into account individual vari-ability in order to choose more accurately which treatment and prevention strategies suit each person. However, drug response prediction for cancer therapy remains a challenge. In this work, we propose a deep neural network model to predict the effect of anticancer drugs in tumors through the half-maximal inhibitory concentration (IC50). The model can be seen as two-fold: first, we pre-trained two autoencoders with high-dimensional gene expression and mutation data to capture the crucial features from tumors; then, this genetic background is translated to cancer cell lines to predict the impact of the genetic variants on a given drug. Moreover, SMILES structures were introduced so that the model can apprehend relevant features regarding the drug compound. Finally, we use drug sensitivity data correlated to the genomic and drugs data to identify features that predict the IC50 value for each pair of drug-cell line. The obtained results demonstrate the effectiveness of the extracted deep representations in the prediction of drug-target interactions, achieving a performance of a mean squared error of 1.07 and surpassing previous state-of-the-art models.