Exploring transcriptomic signatures in sudden unexplained death (SUD) cases

Figures

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  Fig. 1. Heatmap of the top 500 genes with the highest variance. The black frame displays a cluster of samples with a distinct expression pattern, including nine controls that suffered a fast death and one SUD. Red-blue scale: red represents upregulation and blue downregulation

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  Fig. 2. PCA plots of the top 500 genes with highest variance among the 35 SUD and 17 control cases, displaying the first two principal components. A) Samples are separated according to SUD and control, labelled with the sample name. B) SUD samples are divided into the subgroups “primary normal”, “primary cardiomyopathy” (primary_CM) and “secondary condition” (secondary). In addition, the seven SUDEP cases are labelled with a triangle symbol. The samples in the black ellipse are control samples that suffered a fast death and one SUD case (SUDS045)

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  Fig. 3. Heatmap of 1,676 significantly differentially expressed genes between SUD and controls. Samples were annotated to subgroups within SUD (“primary normal”, “primary cardiomyopathy” (primary_CM) and “secondary condition” (secondary)) and controls (“fast death” and “other”). Red-blue scale: red represents upregulation and blue downregulation

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  Fig. 4. Boxplot of normalized read counts in SUD and control samples for the top six DE genes. All genes are upregulated in the SUD samples

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  Fig. 5. Gene expression differences between SUD and control samples with a focus on cardiac related genes. A) Heatmap of the 42 cardiac genes significantly differentially expressed between SUD and control samples. Red-blue scale: red represents upregulation and blue downregulation. B) Volcano plot showing the log2 fold change plotted against the FDR for each gene tested in DESeq2. Differentially expressed genes that have both FDR ≤ 0.1 and a log fold change ≥ 0.5 are marked in red. The 42 significant genes linked to cardiac diseases are labelled. The most upregulated genes are towards the right, the most downregulated genes are towards the left, and the most statistically significant genes are towards the top.

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  Fig. 6. A) Significant KEGG pathways among genes differentially expressed in SUD cases compared to controls (FDR ≤ 0.1), divided into “Disease” and “Signaling/metabolism pathways” and B) the top 10 differentially expressed GO terms (FDR ≤ 0.1) in each of the three categories biological processes, cellular components and molecular function. Red bars represent downregulated terms and green represent upregulated terms. The effective gene set size used in the analysis is indicated by n

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  Fig. 7. Gene expression differences between “primary normal” and control samples. A) Heatmap of the 332 significantly differentially expressed genes. Red-blue scale: red represents upregulation and blue downregulation. B) Volcano plot with DE genes that have both FDR ≤ 0.1 and a log fold change ≥ 0.5 marked in red. The seven significant cardiac genes are labelled. The most upregulated genes are towards the right, the most downregulated genes are towards the left, and the most statistically significant genes are towards the top. C) Boxplot of normalized read counts for the top six most differentially expressed genes. Only one gene (RNF213) overlaps with the genes in Fig. 4 comparing all SUD and control samples. D) Significant KEGG pathways (FDR ≤ 0.1) among the DE genes in the categories “Disease” and “Signaling/metabolism” and E) significant GO terms (FDR ≤ 0.1). Significant GO terms were only found in the category cellular components. Red bars represent downregulated terms. The effective gene set size n is indicated

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  Fig. 8. Gene expression differences between “primary cardiomyopathy” and control samples. A) Heatmap of the 1,652 significantly differentially expressed genes. Red-blue scale: red represents upregulation and blue downregulation. B) Volcano plot with DE genes that have both FDR ≤ 0.1 and a log fold change ≥ 0.5 marked in red. The 48 significant cardiac genes are labelled. The most upregulated genes are towards the right, the most downregulated genes are towards the left, and the most statistically significant genes are towards the top. C) Boxplot of normalized read counts for the top six DE genes. Four of the six genes overlap with the genes in the boxplot in Fig. 4 comparing all SUD and control samples. D) Significant KEGG pathways (FDR ≤ 0.1) in the categories “Disease” and “Signaling/metabolism” and E) the top 10 significant GO terms (FDR ≤ 0.1) in the categories biological processes, cellular components and molecular functions. Red bars indicate terms that are downregulated in “primary cardiomyopathy”, while green bars indicate upregulated terms, and n is the gene set size

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  Fig. 9. Gene expression differences between “secondary condition” and control samples. A) Heatmap of the 98 significantly differentially expressed genes. Red-blue scale: red represents upregulation and blue downregulation. B) Volcano plot with DE genes that have both FDR ≤ 0.1 and a log fold change ≥ 0.5 marked in red. The three significant cardiac genes are labelled. The most upregulated genes are towards the right, the most downregulated genes are towards the left, and the most statistically significant genes are towards the top. C) Boxplot of normalized read counts for the top six DE genes. Three of the six genes overlap with genes in the boxplot in Fig. 4 comparing all SUD and control samples