Biophysical modeling with variational autoencoders for bimodal, single-cell RNA sequencing data

Abstract

Here we present biVI, which combines the variational autoencoder framework of scVI with biophysical models describing the transcription and splicing kinetics of RNA molecules. We demonstrate on simulated and experimental single-cell RNA sequencing data that biVI retains the variational autoencoder’s ability to capture cell type structure in a low-dimensional space while further enabling genome-wide exploration of the biophysical mechanisms, such as system burst sizes and degradation rates, that underlie observations. biVI models the biophysical processes generating nascent and mature single-cell transcriptomes using variational autoencoders.