SHARE-Topic: Bayesian interpretable modeling of single-cell multi-omic data

Abstract Multi-omic single-cell technologies, which simultaneously measure the transcriptional and epigenomic state of the same cell, enable understanding epigenetic mechanisms of gene regulation. However, noisy and sparse data pose fundamental statistical challenges to extract biological knowledge from complex datasets. SHARE-Topic, a Bayesian generative model of multi-omic single cell data using topic models, aims to address these challenges. SHARE-Topic identifies common patterns of co-variation between different omic layers, providing interpretable explanations for the data complexity. Tested on data from different technological platforms, SHARE-Topic provides low dimensional representations recapitulating known biology and defines associations between genes and distal regulators in individual cells.