DRN-CDR: A cancer drug response prediction model using multi-omics and drug features

Abstract

Cancer drug response (CDR) prediction is an important area of research that aims to personalize cancer therapy, optimizing treatment plans for maximum effectiveness while minimizing potential negative effects. Despite the advancements in Deep learning techniques, the effective integration of multi-omics data for drug response prediction remains challenging. In this paper, a regression method using Deep ResNet for CDR (DRN-CDR) prediction is proposed. We aim to explore the potential of considering sole cancer genes in drug response prediction. Here the multi-omics data such as gene expressions, mutation data, and methylation data along with the molecular structural information of drugs were integrated to predict the IC50 values of drugs. Drug features are extracted by employing a Uniform Graph Convolution Network, while Cell line features are extracted using a combination of Convolutional Neural Network and Fully Connected Networks. These features are then concatenated and fed into a deep ResNet for the prediction of IC50 values between Drug – Cell line pairs. The proposed method yielded higher Pearson’s correlation coefficient ($r_p$) of 0.7938 with lowest Root Mean Squared Error (RMSE) value of 0.92 when compared with similar methods of tCNNS, MOLI, DeepCDR, TGSA, NIHGCN, DeepTTA, GraTransDRP and TSGCNN. Further, when the model is extended to a classification problem to categorize drugs as sensitive or resistant, we achieved AUC and AUPR measures of 0.7623 and 0.7691, respectively. The drugs such as Tivozanib, SNX-2112, CGP-60474, PHA-665752, Foretinib etc., exhibited low median IC50 values and were found to be effective anti-cancer drugs. The case studies with different TCGA cancer types also revealed the effectiveness of SNX-2112, CGP-60474, Foretinib, Cisplatin, Vinblastine etc. This consistent pattern strongly suggests the effectiveness of the model in predicting CDR.