Comparative regulatory analysis of single cell data reveals a novel B cell subpopulation in chronic lymphocytic leukemia

We propose a computational method for single cell comparative regulatory analysis based on single cell gene expression (scRNA-seq) and single cell chromatin accessibility data (scATAC-seq) from two different conditions. Our software sc-compReg provides joint clustering and embedding of the cells from both scRNA-seq and scATAC-seq, and construction of differential regulatory networks across two conditions. We apply the method to compare gene regulatory networks in bone marrow mononuclear cells (BMMCs) obtained from a healthy donor and one with chronic lymphocytic leukemia (CLL). The analysis reveals a tumor-specific B cell subpopulation and identifies TOX2 as a novel regulator of this subpopulation. Single cell RNA and single cell ATAC-seq profiles of BMMCs from two donors (CLL, Healthy) ***Raw sequence data is not submitted to a repository to protect the privacy of the anonymous human donors recruited by AllCells***