Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction

Figure 1. Overviews of differential expression analysis. (a) Principal component analysis (PCA) plot of proteomic data in HCM, chronic and HFpEF groups. (b) Heatmap of individual samples with hierarchical clustering dendrogram of proteome profiles across HCM, chronic and acute HFpEF groups. Volcano plots of proteomic data in (c) acute HFpEF vs. HCM, (d) chronic HFpEF vs. HCM, and (e) acute HFpEF vs. chronic HFpEF. Differential expression (DE) analysis was performed by fitting a linear regression model adjusted for age, gender and diabetes. DE proteins were defined as Benjamini–Hochberg adjusted p value < 0.01, as indicated by the proteins above the cut-off lines.

Figure 2. Highlighted proteins in differential expression analysis. (a) Triple Venn diagram summarising the differentially expressed proteins unique and overlapped between chronic HFpEF vs. HCM, acute HFpEF vs. HCM and acute vs. chronic HFpEF. (b) Three-dimensional plot of fold changes (Log2-transformed) of all identified proteins, with a regression plane filled with colour indicator of log2-fold changes.

Figure 3. Pathway analysis. (a) Triple Venn diagram illustrating the number of pathways significantly changed in acute HFpEF vs. HCM, chronic HFpEF vs. HCM and acute HFpEF vs. chronic HFpEF. (b) Representation of all significantly altered pathways between the three comparison groups in order of significance (x-axis is −log10(FDR)); and (c) for the pathway of platelet degranulation in response to elevated platelet cytosolic Ca2+. IGF, insulin-like growth factor; and IGFBP, insulin-like growth factor binding protein.

Figure 4. Network analysis. Network plots illustrating protein–protein interactions in (a) acute HFpEF vs. HCM, (b) chronic HFpEF vs. HCM and (c) acute vs. chronic HFpEF. Each node represents one protein; and each edge represents a pairwise Pearson correlation between proteins. The networks only show Pearson correlation coefficient > 0.7 or <−0.7. Node: colour coded according to the functional classification of proteins annotated by DAVID; size proportional to the corresponding eigenvector centrality (network influence). Edge: colour and length proportional to the Pearson correlation coefficient; width proportional to the scores derived from STRING database.