Fig. 4

Fibroblasts may partially contribute to the cardiac arrhythmia of ARVC. A Log-fold-change and two-sided P-value for expression changes between AC_RV (n = 6) and NC_RV (n = 2) (left), AC_LV (n = 6) and NC_LV (n = 2) (center), and AC_RV and AC_LV (right) hearts for each gene tested using limma–voom differential expression analysis. Genes are colored by cell type with larger, opaque dots representing genes with FDR < 0.01 based on the Benjamini–Hochberg procedure. B The number of significantly differentially expressed genes (FDR < 0.01) by cell type for each comparison in (A). C Reactome pathway enrichment for differential expression between each comparison in (A) by cell type. The size of each square represents a two-sided P-value from GSEA and shading represents the normalized enrichment score (NES). Only pathways with a Benjamini–Hochberg FDR < 0.05 in both the GSEA and hypergeometric test for over-representation in at least one cell type are shown. Pathways with FDR < 0.05 in the GSEA test are denoted with a black outline. D Dot plot showing the number of DEGs per cell type that overlaps as GWAS risk variants across cardiac arrhythmia traits from the GWAS catalog (NHGRI-EBI) [39]. Significance of overlap is based on FDR < 0.05. GSEA, gene set enrichment analysis; NES, normalized enrichment score; FDR, false discovery rate; ARVC, arrhythmogenic right ventricular cardiomyopathy; NC, normal control; AC_LV, left ventricle of ARVC; AC_RV, right ventricle of ARVC; NC_LV, left ventricle of NC; NC_RV, right ventricle of NC; AC_PBMC, PBMC of ARVC; PBMC, peripheral blood mononuclear cell; NK, natural killer; NP, neutrophils; VSMC, vascular smooth muscle cell; DEGs, differentially expressed genes