Predicting drug activity against cancer through genomic profiles and SMILES.

ABSTRACT

Due to the constant increase in cancer rates, the disease has become a leading cause of death worldwide, enhancing the need for its detection and treatment. In the era of personalized medicine, the main goal is to incorporate individual variability in order to choose more precisely which therapy and prevention strategies suit each person. However, predicting the sensitivity of tumors to anticancer treatments remains a challenge. In this work, we propose two deep neural network models to predict the impact of anticancer drugs in tumors through the half-maximal inhibitory concentration (IC50). These models join biological and chemical data to apprehend relevant features of the genetic profile and the drug compounds, respectively. In order to predict the drug response in cancer cell lines, this study employed different DL methods, resorting to Recurrent Neural Networks (RNNs) and Convolutional Neural Networks (CNNs). In the first stage, two autoencoders were pre-trained with high-dimensional gene expression and mutation data of tumors. Afterward, this genetic background is transferred to the prediction models that return the IC50 value that portrays the potency of a substance in inhibiting a cancer cell line. When comparing RSEM Expected counts and TPM as methods for displaying gene expression data, RSEM has been shown to perform better in deep models and CNNs model can obtain better insight in these types of data. Moreover, the obtained results reflect the effectiveness of the extracted deep representations in the prediction of the IC50 value that portrays the potency of a substance in inhibiting a tumor, achieving a performance of a mean squared error of 1.06 and surpassing previous state-of-the-art models.