Ubiquitin-specific protease as the underlying gene biomarker for aortic stenosis

Figures

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  Fig. 1. Differential expression analysis and WGCNA analysis of the genes in the merged series. a Volcano plots of the genes which are different expression (DEGs) between aortic valve stenosis group and normal group. b The cluster of patients with clinical information, red line represents patients with aortic valve stenosis. c The lowest power for which scale independence. d Repeated hierarchical clustering tree of the 9636 genes.e The dendrogram and heatmap of genes. f Interactions between these modules. g The associations between clinic traits and the modules. h Heatmaps of the 83 DEGs in the MEdarkgrey model

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  Fig. 2. Gene functional enrichment analysis of the MEdarkgrey model DEGs by GSEA and Metascape. a Gene ontology (GO) analyses by GSEA. b Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of by GSEA. c Enrichment_GO-KEGG_ColorByCluster analyses by Metascape. d Enrichment_GO-KEGG_ColorByPValue analyses by Metascape. e Enrichment_heatmap_HeatmapSelected GO-KEGG analyses by Metascape

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  Fig. 3. Relationship between DEGs. a Protein-protein interaction (PPI) network, the more the number of connections, the larger of the protein. The orange was defined as dark color to map parameters, which represented the high value of protein. The yellow was defined as middle color to map parameters, which presented the middle value of protein. The blue was defined as bright color to map parameters, which represented the low value of protein. The small sizes showed the low values, and the large sizes represented the high values. b The common hub genes identified from different algorithm. c The common hub genes of protein-protein interaction network. d Heat maps of the common hub genes

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  Fig. 4. Relationship to aortic valve stenosis group and normal group related to DEGs based on the CTD database. The blue column represented the inference score, and the red column represented the references

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  Fig. 5. Functional and pathway enrichment analysis of miRNAs which could regulate hub genes. a BP analyses (b) CC analyses. c MF analyses. d KEGG analyses of the miRNAs. BP: biological processes, CC: cellular component, MF: molecular functions, KEGG: Kyoto Encyclopedia of Genes and Genomes

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  Fig. 6. ROC curves of hub genes

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  Fig. 7. Histological patterns of aortic valve through HE staining

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  Fig. 8. The expression level of USP14 in the histology via immunohistochemistry assay

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  Fig. 9. The detection of USP14 content of the aortic valve by immunofluorescence assay

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  Fig. 10. Verification of the expression of USP14 in the mRNA and protein level. a Relative expression of USP14 by RT-qPCR analysis. *p < 0.05, compared with control. b, c Western blotting expression of USP14 in the control and aortic stenosis groups