Transcriptome of human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71

Figures

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  Figure 1. Volcano plots of the differentially expressed genes (DEGs) in each comparison group including 2BmCherry versus SHSY5Y transcriptome (a) mCherry versus SHSY5Y transcriptome (b), and 2BmCherry versus mCherry transcriptome (c). The x-axis represents the magnitude of statistical significance. The y-axis indicates the magnitude of change. The dash line indicates a threshold of significant magnitude at -log10(p-adj) = 1.3 or p-adj < 0.05.

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  Figure 2. Unsupervised hierarchical heatmap clustering with double-dendrogram of the patterns of significant differences of DEGs among the three transcriptomes. DEGs are clustered in roll of each transcriptome displayed on the column. The gradient colors indicate the magnitude of changes in the gene expression levels, red color for upregulation and blue color for downregulation. Dendrogram on the top indicates a cluster of the genes with similar expression levels. Dendrogram on the left site indicates a similarity of the expression pattern across the transcriptome.

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  Figure 3. Venn diagrams of upregulated (a) and downregulated (b) DEGs among the three comparison groups (2BmCherry versus SHSY5Y, mCherry versus SHSY5Y, and 2BmCherry versus mCherry). The numbers in the overlap areas indicate the common DEGs found in the compared transcriptomes. The numbers in the non-overlap areas indicate the unique DEGs of the respective transcriptomes.

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  Figure 4. The bar charts of the significant GO categories enriched by the upregulated (a) and the downregulated (b) DEGs in the 2BmCherry transcriptome. The x-axis represents the name of a certain GO term. The y-axis refers to the number of the genes enriched in the term.

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  Figure 5. Diagram depicts the protein–protein interaction (PPI) network of the unique DEGs in the 2BmCherry transcriptome. The circles represent the protein nodes, the bigger size indicates the higher magnitude of statistical significance. The colors indicate the magnitude of changes, the log2(fold changes); red color indicates the upregulation, blue color indicates the downregulation, and green color indicates the undetermined fold change. The significant nodes are indicated by arrowheads. The light-to-dark grey colors of the connected lines indicate the increment of confidence of interaction (combined score 0.700–0.999). The nodes in the box show the biggest network.

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  Figure 6. Diagram depicts the sub-network of the protein hubs and their first-neighboring interactors. The gradient color of yellow-to-red of the protein nodes indicates increment of the degree value for being the hub. The pale green nodes refer to the first-neighboring interactor in the network. The light-to-dark grey color of the connected lines indicates the confidence value of interaction (0.700–0.999). There are 4 clusters of nodes in which each of them is composed of DEGs involved in the regulation of gene expression (a), RNA processing (b), cell survival and cell death (c), and (d) protein degradation which indicated by the separate circles.

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  Figure 7. Summary of major upregulated genes and biological pathways in human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71 (EV-A71). The EV-A71 2B protein increases cytosolic calcium (Ca2+). The aberrant level of cytosolic Ca2+ triggers Ca2+-related signaling pathways participating gene expression, apoptosis, inflammatory response, non-canonical NF-κB signal transduction, and long-term potentiation of neuron. CCL2, IL32, PLAT, PTGES, and PHLDA1 are associated with neuroinflammation. The EV-A71 2B might activate non-canonical NF-κB signaling pathway through TNFRSF9, BIRC3, and RelB by unidentified mechanism which lead to expression of CCL2.