Identification of Crucial Genes and Pathways in Human Arrhythmogenic Right Ventricular Cardiomyopathy by Coexpression Analysis

Figures

• 

  FIGURE 1. Study flow diagram. Data preparation, processing, and analysis are shown in the flow diagram.

• 

  FIGURE 2. Clustering dendrogram and the clinical traits, as well as identification of differentially expressed genes (DEGs) in ARVC tissues. (A) Clustering dendrogram and clinical traits of GSE29819. The clustering was on the basis of the expression data of DEGs between ARVC samples and non-failing donor myocardial samples. The red color represents the right ventricle and men. The color intensity was in proportion to the older age. (B) The volcano plot of all DEGs.

• 

  FIGURE 3. (A) Heatmap showing significantly differentially expressed protein-coding genes of ARVC and non-failing donor myocardial tissues. In the heatmap, samples are sorted by columns, and genes by rows. Cyan square represented Control group, and red square represented ARVC group. (B) PCA scores trajectory plots showing obvious differences resulting from the ARVC and Control groups. Cyan point, control group; red point, ARVC group.

• 

  FIGURE 4. Determination of soft-threshold power in WGCNA. The scale-free topology index and the mean connectivity for each power value between 1 and 20 are shown in (A,B) panels, respectively. The histogram of connectivity distribution and the scale-free topology are shown in (C,D) panels, respectively.

• 

  FIGURE 5. Identification of modules related to the clinical traits of the ARVC. (A) Dendrogram of all differentially expressed genes clustered on the basis of one dissimilarity measure (1-TOM). (B) Heatmap of the correlation between module eigengenes and ARVC clinical traits. (C) Distribution of the mean gene significance and errors in the modules related to ARVC state. Barplot of module significance (MS) defined as the average gene significance across all genes in modules.

• 

  FIGURE 6. Scatterplots showing gene significance versus module membership for the brown (A) and turquoise (B) modules.

• 

  FIGURE 7. MST2s plot of the four key pathways correlation network. This plot was produced by package GSAR to illustrate the most highly correlated pathways and their hub genes of the two modules in both control samples and ARVC samples. Four ARVC state related biological pathways were identified by GSNCA (A–D).

• 

  FIGURE 8. Hub genes validation. (A) Violin plot of the four correlated hub genes (C5AR1, CXCL2, LIFR, and TNFRSF11B) expression between ARVC group and control group. The violin plot showed the mean value, median value (while circle and black horizontal band, respectively), and range (black thin vertical line). The curve on the sides provided the approximate frequency distribution at each expression level. The p-values of the t-test were marked on the black lines. (B) ROC curves and AUC areas were used for evaluating the efficiency of diagnosis of these four hub genes (C5AR1, CXCL2, LIFR, and TNFRSF11B). They all be with high AUC areas (AUC > 0.8).