Isolating salient variations of interest in single-cell data with contrastiveVI

Single-cell datasets are routinely collected to investigate changes in cellular state between control cells and the corresponding cells in a treatment condition, such as exposure to a drug or infection by a pathogen. To better understand heterogeneity in treatment response, it is desirable to deconvolve variations enriched in treated cells from those shared with controls. However, standard computational models of single-cell data are not designed to explicitly separate these variations. Here, we introduce contrastive variational inference (contrastiveVI; https://github.com/suinleelab/contrastiveVI ), a framework for deconvolving variations in treatment-control single-cell RNA sequencing (scRNA-seq) datasets into shared and treatment-specific latent variables. Using three treatment-control scRNA-seq datasets, we apply contrastiveVI to perform a variety of analysis tasks, including visualization, clustering and differential expression testing. We find that contrastiveVI consistently achieves results that agree with known ground truths and often highlights subtle phenomena that may be difficult to ascertain with standard workflows. We conclude by generalizing contrastiveVI to accommodate joint transcriptome and surface protein measurements.