TooManyPeaks Identifies Drug-resistant-specific Regulatory Elements From Single-cell Leukemic Epigenomes.
Schwartz WG, Zhou Y, Petrovic J, Pear WS, Faryabi RB

Cell Reports


Emerging single-cell epigenomic assays are used to investigate the heterogeneity of chromatin activity and its function. However, identifying cells with distinct regulatory elements and clearly visualizing their relationships remains challenging. To this end, we introduce TooManyPeaks to address the unmet need for the simultaneous study of chromatin state heterogeneity in both rare and abundant subpopulations. Our analyses of existing data from three widely used single-cell assays for transposase-accessible chromatin using sequencing (scATAC-seq) showed the superior performance of TooManyPeaks in delineating and visualizing pure clusters of rare and abundant subpopulations. Furthermore, the application of TooManyPeaks to new scATAC-seq data from drug-naive and drug-resistant leukemic T cells clearly visualized relationships among these cells and stratified a rare “resistant-like” drug-naive sub-clone with distinct cis-regulatory elements.