Unsupervised deep learning with variational autoencoders applied to breast tumor genome-wide DNA methylation data with biologic feature extraction

Recent advances in deep learning, particularly unsupervised approaches, have shown promise for furthering our biological knowledge through their application to gene expression datasets, though applications to epigenomic data are lacking. Here, we employ an unsupervised deep learning framework with variational autoencoders (VAEs) to learn latent representations of the DNA methylation landscape from three independent breast tumor datasets. Through interrogation of methylation-based learned latent dimension activation values, we demonstrate the feasibility of VAEs to track representative differential methylation patterns among clinical subtypes of tumors. CpGs whose methylation was most correlated VAE latent dimension activation values were significantly enriched for CpG sparse regulatory regions of the genome including enhancer regions. In addition, through comparison with LASSO, we show the utility of the VAE approach for revealing novel information about CpG DNA methylation patterns in breast cancer.