Divergent Atrial Transcriptomic Signatures in Diabetic and Nondiabetic Atrial Fibrillation

Figures

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  FIGURE 1. Volcano plot of all expressed protein‐coding genes in the right atrial appendage obtained from RNA sequencing, where the x‐axis denotes log2 fold change and the y‐axis denotes –log10 p‐value. Vertical red lines represent fold changes of 1/1.5 and 1.5, and the horizontal red line represents p = 0.05. Red and green dots indicate up‐ and downregulated genes, respectively. (B) Volcano plot of protein‐coding genes with fold change < 1/1.5 or > 1.5 and p < 0.05. Dot size represents mean expression calculated as log2(TPM + 1). (C) Volcano plot of all expressed microRNAs. Vertical and horizontal red lines are as in (A). Red dots represent upregulated and green dots represent downregulated microRNAs. (D) Volcano plot of microRNAs with fold change < 1/1.5 or > 1.5 and p < 0.05. Dot size represents mean expression calculated as log2(TPM + 1).

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  FIGURE 2. Top 20 results of Gene Ontology (GO) enrichment analysis for differentially expressed genes selected with fold change thresholds of 1/1.2 and 1.2 and p < 0.05. (B) Gene‐concept network of the top 20 GO terms and their associated genes. Red and blue small nodes represent up‐ and downregulated genes, respectively, while large orange nodes represent GO terms. Node size reflects the number of linked genes. BP, Biological process; CC, Cellular component; MF, Molecular function.

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  FIGURE 3. Top 20 upregulated (A) and down regulated gene sets (C) identified by Gene Set Enrichment Analysis (GSEA), ranked by normalized enrichment score (NES). Representative enrichment plots of the first and second most significantly upregulated (B) and downregulated gene sets (D). The top panel (green line) shows the running enrichment score. The middle panel (black ticks) indicates the positions of gene set members in the ranked gene list, where the red side represents top‐ranked and the blue side bottom‐ranked genes in the DM group. The bottom panel (gray bars) shows the ranking metric values (“signal‐to‐noise”).

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  FIGURE 4. Enrichment map generated from GSEA results. Nodes represent gene sets, and edges indicate shared genes between nodes. Clusters of related gene sets were generated using the AutoAnnotate app. Cluster names were refined with reference to the GO graph from the Gene Ontology website (https://www.geneontology.org/).

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  FIGURE 5. (A, B) Comparison of our data with animal experimental data from the Gene Expression Omnibus (GSE161931 and GSE197999). For the mouse model (GSE161931: Db/db vs. control), fold‐change thresholds were 1/1.2 and 1.2 with p < 0.05. For the rat model (GSE197999: STZ‐induced vs. control), thresholds were 1/1.5 and 1.5 with p < 0.05. (C) Comparison of gene expression between mouse (GSE161931) and rat (GSE197999) models, with thresholds of 1/1.2 and 1.2 and p < 0.05 for both. Gene symbols: ACAA2, acetyl‐CoA acyltransferase 2; ACER2, alkaline ceramidase 2; ACOT1, acyl‐CoA thioesterase 1; ACOT2, acyl‐CoA thioesterase 2; ANGPTL4, angiopoietin‐like 4; BST2, bone marrow stromal cell antigen 2; C2, complement C2; C3, complement component 3; CD74, CD74 molecule; CIDEA, cell death‐inducing DNA fragmentation factor, alpha subunit‐like effector A; CP, ceruloplasmin; CRIP2, cysteine rich protein 2; DECR1, 2,4‐dienoyl‐CoA reductase 1; ECH1, enoyl CoA hydratase 1; ECI1, enoyl‐Coenzyme A delta isomerase 1; EPB41, erythrocyte membrane protein band 4.1; FBLN1, fibulin 1; FGF18, fibroblast growth factor 18; GCAT, glycine C‐acetyltransferase; GPAT3, glycerol‐3‐phosphate acyltransferase 3; GPC3, glypican…