Extended Data Fig. 6: Independent evaluation of GRN33, GRN195 and GRN122 cell-specificity, reproducibility and roles in atherosclerotic cardiovascular disease.
a) GRN33 (top), GRN195 (middle) and GRN122 (bottom) cell-type specificity according to the enrichment of cell-type determined genes in scATAC-seq data obtained from 41 human coronary artery tissue samples (Methods). Dot plots show odds ratio of enrichment of GRN33, GRN195 and GRN122 module genes for marker genes determined from integrated snATAC-seq and scRNA-seq profiles obtained from atherosclerotic coronary artery tissues30 (Methods). b) GRN33 (top), GRN195 (middle) and GRN122 (bottom) reproducibility according to NetRep31. The original GRN33 connectivity in bulk RNAseq data from the atherosclerotic aortic wall in STARNET was compared with that of two bulk coronary (UVA and GTEx), primary blood MP cell (STARNET)5, and one additional primary blood MP (NGS-PREDICT, Ma et al., unpublished) RNAseq datasets filtered for female donors. The original GRN195 connectivity in bulk RNAseq data from the atherosclerotic aortic wall in STARNET was compared with that of two coronary (UVA and GTEx) and one human aortic endothelial cell (HAEC) RNAseq datasets, the latter filtered for male donors57. The original GRN122 connectivity in bulk RNAseq data from the atherosclerotic aortic wall in STARNET was compared with that of bulk coronary and aorta (GTEx), primary blood MP cell (STARNET)5, and one additional primary blood MP (NGS-PREDICT, Ma et al., unpublished). RNAseq datasets filtered for female donors. ‘cor.cor´ measures the concordance of correlation structures; ‘cor.degree´ measures the concordance of the weighted degrees; ‘cor.contrib´ measures the concordance of node contributions; ‘avg.cor’ measures the average magnitude of correlation coefficients and ‘avg.contrib´ measures the average magnitude of node contributions. The bar shows log−10 P-values. P-values were adjusted for multiple testing using the Benjamini & Hochberg method. c) Barplots showing the odds ratio (OR) for GRN33 (top), GRN195 (middle) and GRN122 (bottom) enrichments in coronary artery differential expressed genes comparing (1) lesions (n = 28) versus non-lesions (n = 26), (2) ischemic (n = 38) versus non-ischemic (n = 23) heart explants, and (3) combined lesion and ischemic (Methods). The Fisher test was performed on overlapping gene sets, the p-values shown represent the Fischer test (two-tailed) p-values and error bars represent 95% confidence intervals. Data represent Mean ± SEM.
