Metabolic Variation Dictates Cardiac Pathogenesis in Patients With Tetralogy of Fallot

Figures

• 

  Figure 1. Workflow of metabolic reprogramming analysis.

• 

  Figure 2. Differentially expressed gene (DEG) identification and functional enrichment analysis. (A) Volcano plot showing DEG distribution. (B) Clustering heatmap and biological analysis presenting the biological function of up- and downregulated DEGs. (C) Biological function terms based on gene ontology were calculated by the GSEA algorithm in response to the comparison between ToF and ASD RA specimens.

• 

  Figure 3. Metabolic pathway detection and interaction network construction. (A) Clustering heatmap showing GSVA-quantized pathway score of metabolic maps. (B) Metabolic map interaction analysis was identified via weighted partial correlation analysis. (C) Differential analysis of metabolic pathways of GSVA score in Figure 2C. (D) Three-dimensional principal component analysis, showing right atrial biopsy sample distribution of ToF and ASD patients before cardiopulmonary bypass. (E) Clustering heatmap depicting the standard quantification of metabolites in ToF and ASD RA specimens. #p < 0.05.

• 

  Figure 4. Detection of differentially expressed metabolites in ToF and ASD RA specimens via the UPLC–MS/MS spectra. (A) T-score of OPLS-DA showing the distribution of ToF and ASD specimens. (B) Volcano plot showing the distribution of differentially expressed metabolites. (C) Differential expression of metabolites in ToF and ASD specimens. (D) Scatter diagram of Figure 3D showing the standardized Z-score for each sample.

• 

  Figure 5. Pathway enrichment analysis with differentially expressed metabolites. (A) The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis involved in classification of environmental information processing, metabolism, and cellular processes were identified. (B) Of the biologic procession, the significantly enriched terms were identified in Figure 4B. (C) Metabolic pathway enrichment was detected based on metabolite set enrichment analysis. (D) Overlap between the gene list involved in butanoate metabolism and DEGs of GSE132176.

• 

  Figure 6. Hub regulator expression and functional enrichment analysis of ToF and ASD RA specimens. (A,B) Hub genes showed differences in ToF and ASD RA specimens in the GSE132176 and GSE169214 datasets, respectively. (C) Hub terms were enriched in response to hub regulators. #p < 0.05.