Fig. 5: Proteo-transcriptional architecture of human aortic stenosis.

UMAP of cell types (A) and condition (B) defined by single-nuclear RNA-sequencing (114,288 nuclei across 7 broad clusters). C Cell composition by condition identifies a significant increase in endothelial cells in AS hearts; *** represents significance. D Heatmap representing the differentially expressed genes associated with remodeling across pseudobulk and cell-specific analyses. Numbers adjacent to the cell type label represent the total number of significant genes, inclusive of those which overlap across comparisons. E Select terms from Gene Ontology analysis of differentially expressed genes associated with remodeling, which highlight cell type-specific pro-angiogenic and pro-inflammatory processes. Full tabular results for all analyses are available in Supplementary Data 9. F Quantile-quantile plot showing the association of genetically determined circulating protein expression with HF. A leftward shift from the gray line shows departure from the null (standard uniform) distribution. The red dashed line denotes \(P < 0.05\). The protein IL15RA is shown twice as it is tagged by 2 SOMAmers, each of which shows an association with HF. G Quantile-quantile plot showing the association of genetically determined gene expression in the left ventricle with HF. A leftward shift from the gray line shows departure from the null (standard uniform) distribution. The red dashed line denotes \(P < 0.05\). Note MIF, HEXIM1, and ANXA4 also show \(P < 0.05\) in the association between the genetic component of the respective protein expression and HF. Source data are provided as a Source Data file.