Fig. 4: Single-cell EpiChem enables dynamic mapping of JQ1-btn genomic binding and its target BRD4 engagement in human CRC organoids.
From: Single-cell EpiChem jointly measures drug–chromatin binding and multimodal epigenome
a, UMAP showing scEpiChem (JQ1-btn, BRD4 and ATAC) in human CRC organoids (n = 19,983), identified as epithelial cells (n = 10,981) and Intermediate EMT cells (n = 9,004). b, The pseudotime trajectory of the EMT progression. c, UMAP projections showing the gene activity scores of VIM and CDH1. d, Heatmaps showing dynamic genomic signals of BRD4 and JQ1 along the pseudotime. Rows were clustered by hierarchical co-clustering and smoothed by the step size of one. Representative genes in each cluster were labeled on the right. e, Top five enriched GO terms of each small molecule (C1:1,384, C2:3,615, C3:2,917) are shown on the right. The P values of GO term enrichment analysis were calculated using a hypergeometric test, with two-sided statistical tests and adjustments for multiple comparisons employing the Benjamini–Hochberg method. f, Violin plots showing Cramér’s V of association between JQ1-btn + BRD4 (median 0.69), JQ1-btn + ATAC (median 0.48), BRD4 + ATAC (median 0.51) in epithelial cells (n = 10,981); and JQ1-btn + BRD4 (median 0.71), JQ1-btn + ATAC (median 0.50), BRD4 + ATAC (median 0.47) in Intermediate EMT cells (n = 9,004) and JQ1-btn + random (n = 1,261, median 0.03). The same number of simulated random genomic regions (42,782) as for BRD4 peaks was used.
