Fig. 6: ASXL1^MT CMML is associated with increased intratumoral heterogeneity secondary to an extended repertoire of accessible distal enhancers.

a Scatter plot showing 12192 single cells from CMML patients (stratified by ASXL1 genotype) in two-dimensional tSNE space, clustered based on the accessibility of known transcription factor motifs. b Bar graphs and dot plot demonstrating the increased single-cell accessibility of binding sites for 476 transcription factors (top panel), ranked by the difference in accessible transcription factor motif (TFM) binding sites (scATAC-seq peaks with a given transcription factor motif) between ASXL1^WT and ASXL1^MT CMML. The top 50 transcription factors with increased accessible binding sites are magnified (bottom panel) and included key oncogenic myeloid transcription factors such as MZF1, MEF2C, and MEIS1. Source data are provided as a Source Data file. c Area graphs and box plots showing a measure of tissue diversity (based on single-cell entropies) for 12192 single cells from CMML patients (stratified by ASXL1 genotype). The two-sample Kolmogorov-Smirnov test for equality of distribution functions was used to compare both distributions. Source data are provided as a Source Data file. d Area graphs and box plots showing a measure of tissue specialization (based on single-cell entropies) for 12192 single cells from CMML patients (stratified by ASXL1 genotype). The two-sample Kolmogorov-Smirnov test for equality of distribution functions was used to compare both distributions (p-value). Source data are provided as a Source Data file. e Bar graphs showing the enrichment of ETS transcription factor motifs in 1504 ASXL1^MT-specific distal enhancers identified by scATAC-seq (validation of bulk ATAC-seq findings). Data are presented as standard Tukey boxplots (with the box encompassing Q1 to Q3, the median denoted as a central horizontal line in the box, and the whiskers covering the data within ±1.5 IQR in 6c and d).