Predicting chemotherapy response using a variational autoencoder approach

Abstract

MotivationMultiple studies have shown the utility of transcriptome-wide RNA-seq profiles as features for machine learning-based prediction of response to chemotherapy in cancer. While tumor transcriptome profiles are publicly available for thousands of tumors for many cancer types, a relatively modest number of tumor profiles are clinically annotated for response to chemotherapy. The paucity of labeled examples and high dimension of the feature data limit performance for predicting therapeutic response using fully-supervised classification methods. Recently, multiple studies have established the utility of a deep neural network approach, the variational autoencoder (VAE), for generating meaningful latent features from original data. Here, we report first study of a semi-supervised approach using VAE-encoded tumor transcriptome features and regularized gradient boosted decision trees (XGBoost) to predict chemotherapy drug response for five cancer types: colon adenocarcinoma, pancreatic adenocarcinoma, bladder carcinoma, sarcoma, and breast invasive carcinoma. ResultsWe found: (1) VAE-encoding of the tumor transcriptome preserves the cancer type identity of the tumor, suggesting preservation of biologically relevant information; and (2) as a feature-set for supervised classification to predict response-to-chemotherapy, the unsupervised VAE encoding of the tumors gene expression profile leads to better area under the receiver operating characteristic curve (AUROC) classification performance than either the original gene expression profile or the PCA principal components of the gene expression profile, in four out of five cancer types that we tested. Availabilitygithub.com/ATHED/VAE_for_chemotherapy_drug_response_prediction Contactramseyst@oregonstate.edu Supplementary informationSupplementary data are available at Bioinformatics online.