Fig. 7: Enrichments of sex-diversified EC subcluster genes in human GRNs.
a, Dot plot showing 15 top-ranked arterial wall GRNs (x axis) according to their enrichments in genes of sex-specified EC subclusters in the carotid plaques. The y axis shows −log(10% FDR) (highlighted). Dot size indicates the number of genes overlapping between EC subclusters and GRNs. b, Horizontal bar graph showing the statistical enrichments (x axis, −log10(P value)) of genes associated with SYNTAX scores of the arterial-wall-specific GRNs above −log(10% FDR) in a. c, Horizontal bar graph showing the statistical enrichments (x axis, −log10(P value)) of genes associated with Duke scores in the arterial-wall-specific GRNs above −log(10% FDR) in a. d, Horizontal bar graph showing the enrichment significances (x axis, −log10(P value)) of DEGs in indicated EC subclusters between symptomatic and asymptomatic carotid plaques in the arterial-wall GRNs above −log(10% FDR) in a. e, Horizontal bar graph showing the enrichment significances (x axis, −log10(P value)) in indicated EC subclusters of DEGs in Athero-Express scRNA-seq carotid plaque data55 between 20 females and 26 males in the arterial-wall GRNs above −log(10% FDR) in a. f, Pie chart showing the relative cell type specificity of genes in GRN195 (top) and GRN122 (bottom) according to the scRNA-seq data (Methods). Below the pie chart are abbreviations of GRN195 (top) and GRN122 (bottom) GWAS CAD candidate genes. g, GRN195 (top) and GRN122 (bottom) color coded according to the cell type specificity. Bigger-sized nodes are key driver genes. h, Bar plot (left) showing sex-specific expression of top-ranked key drivers isolated from female (n = 7) and male (n = 8) carotid plaques and (right) corresponding expression patterns during the progression of atherosclerosis in female (n = 18) or male (n = 28) Ldlr−/−Apob100/100 mice (Methods). Top or rank, key driver’s hierarchical ranking in the GRN. H2, broad sense heritability contributions of GRN (%). The green center line denotes the median value (50th percentile), and the green box contains the 25th to 75th percentiles of the dataset. The green whiskers mark the 5th and 95th percentiles. i, Radar plot showing the statistical significance of key cardiometabolic phenotype associations with GRN195 (top) and GRN122 (bottom). The significance of GRN–phenotype associations (−log10; P = 0–100) was calculated by aggregating GRN gene–level phenotype associations (Pearson correlation two-tailed t-test) corrected for the total number of STARNET GRNs (n = 135) and the number of genes in each GRN using the Benjamini–Hochberg procedure.
