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Fig. 4 | Genome Biology

Fig. 4

From: EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data

Fig. 4

EPISCORE reveals epigenetic remodeling of endothelial cells in lung cancer. a Landscape barplot of CellDMC’s predictions for the number of lung-cancer associated DMCTs (y-axis) in each of the 4 major cell types, and their overlaps, as indicated beneath the barplots. For instance, there were 450 DMCTs occurring in both endothelial and epithelial cells and only 1 CpG commonly differentially methylated across all 4 cell types. Red barplots indicate highly significant overlaps of DCMTs occurring in respective cell types. b Four examples of DMCTs, two in the epithelial and two in the endothelial compartment. Each scatterplot displays the DNAm beta value adjusted for cell type fractions (y-axis) vs. the estimated fraction of the relevant cell type (x-axis). Specific CpG and associated t statistic P value of the DMCT are given. N, normal samples (blue); C, cancer samples (red). c Scatterplot of statistical significance (− log10P, y-axis) vs. logged odds ratio (log2OR, x-axis) for biological terms enriched among the epithelial (left) and endothelial (right) DMCTs respectively. Green dashed line indicates the line FDR < 0.05. Blue (orange) denote biological terms enriched among cancer hypermethylated (hypomethylated) DMCTs. d For each of the main cell types (epithelial, endothelial, fibroblast, and immune cell), scatterplot of the t statistics from CellDMC comparing LSCC to normal-adjacent lung tissue (x-axis) vs. the corresponding t statistics comparing LUAD to normal-adjacent lung tissue (y-axis). CpGs that show consistent significant cell type-specific hypermethylation (hypomethylation) between the two TCGA lung cancer studies are displayed in blue (orange). P value is from a one-tailed Fisher test assessing the statistical significance of the correlation. Green dashed lines correspond to the FDR < 0.05 line, as determined in the LSCC study. e Bean density plots of SMAD2 ChIP-Seq binding intensity values in HUVEC endothelial cell line for hypermethylated endothelial DMCT genes in LSCC (red) vs. genes not associated with any DMCTs. Binding peaks falling within a ± 5 kb window of a gene’s TSS was used to assign peaks to genes. P value is from a one-tailed Wilcoxon rank sum test. Horizontal lines indicate the median values in each group. Barplots display the corresponding − log10[P values] of a one-tailed Wilcoxon rank sum test for genes belonging to each of the main DMCT categories. Results are shown for SMAD2 binding targets defined at 3 different window sizes (± 1 kb, ± 5 kb, ± 10 kb). Green dashed line denotes the line P = 0.05

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