TooManyPeaks identifies drug-resistant-specific regulatory elements from single-cell leukemic epigenomes [ATAC-seq]

Purpose: To characterize epigenomic heterogeneity in GSI-responsive and -resistant T-ALL cells Method: We generated GSI-resistant T-ALL DND41 cells and profiled their epigenome using single-cell RNA sequencing. Result: We report here the presence of resistant-like subpopulation in drug naïve DND41 T-ALL cells. Conclusion: While other popular scRNA-seq clustering algorithms failed, TooManyPeaks, a suite of clustering and visualization algorithm developed in our lab, could identify rare resistant-like DND41 T-ALL cells. Overall design: Single-cell ATAC-seq was performed on cells acquiring resistance to a gamma secretase inhibitor (GSI) after long-term treatment of Notch-mutated T-cell acute lymphoblastic leukemia (T-ALL) DND41 cells.