Extended Data Fig. 3: Comparison of failing heart differentially expressed genes defined by CAGE and ChIP-seq data.

a. Differential affinity analysis for Gilsbach et al. ChIP-seq active marks H3K4me3, H3K27ac. The number of defined differential TREs (FDR < 0.05) enriched in failing samples is much lower than in healthy samples, which is consistent with our observation of differential expression analysis (Fig. 2b,c). b. Differentially expressed TREs of failing samples have higher coverage by ChIP-seq active marks compared to healthy samples (likelihood ratio test, multiple testing corrected with Benjamini-Hochberg). Atrial and ventricular differentially expressed TREs have similar coverage. Example genes with consistent profiles in both CAGE and ChIP-seq data are shown as boxplots (CAGE healthy (n = 76) and failing (n = 33); H3K4me3 healthy (n = 3) and failing (n = 3); H3K27ac healthy (n = 2) and failing (n = 3)). The center line of the boxplot shows median, box bounds are first and third quartiles, whiskers indicate minima and maxima, and points show outliers. c. Coverage (CPM normalized) of CAGE TRE by ChIP-seq active marks (H3K4me3, H3K27ac) from Gilsbach et al. To note, there are two samples with a relatively low numbers of reads, SRR6426245 H3K27ac and SRR6426272 H3K4me3, and they appear as outliers on the heatmaps and principal component analysis plots on panel a. RLE - relative log expression, TPM - tags per million, CPM - counts per million.