IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA

Figures

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  Figure 1. The schematic block diagram of the entire workflow of this study.

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  Figure 2. DEGs identification. (A) Gray dots represent genes not substantially differently expressed in RA and HC groups (P > 0.05), red triangles represent upregulated genes (P < 0.05), and green triangles represent downregulated genes (P < 0.05) in the GSE93272 dataset. (B) Gray dots represent genes not substantially differently expressed in S. aureus and HC groups (P > 0.05), red triangles represent upregulated genes (P < 0.05), and green triangles represent downregulated genes (P < 0.05) in the GSE33341 dataset.

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  Figure 3. DEG distribution. (A) The clustering heat map shows the DEGs in the GSE93272 dataset. The RA group’s samples are colored blue, whereas the HC group’s samples are colored red. Red rectangles indicate elevated genes (P < 0.05), whereas blue rectangles indicate downregulated genes (P < 0.05). (B) The clustering heat map shows the intersection of DEGs in the GSE33341 dataset. The SA group’s samples are colored blue, whereas the HC group’s samples are colored red. Red rectangles indicate elevated genes (P < 0.05), whereas blue rectangles indicate downregulated genes (P < 0.05).

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  Figure 4. Common DEG screening. (A) Venn diagram on GSE93272 DEGs and GSE33341 DEGs. (B) Clustered heat map of common DEGs belonging to the RA group. (C) Clustered heat map of common DEGs in the SA group, with the RA/SA group colored blue and the HC group colored red. Red rectangles indicate elevated genes (P < 0.05), whereas blue rectangles indicate downregulated genes (P < 0.05).

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  Figure 5. Functional enrichment analysis: GO, KEGG, and ClueGO analysis of DEGs. (A) BP gene enrichment of DEGs. (B) CC gene enrichment of DEGs. (C) MF gene enrichment of DEGs. (D) Analysis of DEGs using KEGG. (E) Analysis of DEGs using ClueGO.

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  Figure 6. PPI interworking networks. (A) PPI network with 184 nodes and 750 edges. The green hexagon in the lower right corner is the top 10 hub genes derived using the CytoHubba analysis method. (B) Analysis of the top 10 hub genes with CytoHubba of Cytoscape.

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  Figure 7. Functional enrichment analysis: Metascape and GeneMANIA of top 10 hub genes. (A) Pathway and process richness analysis of the Metascape platform. (B) Summary of enrichment analysis of DisGeNET 13 on Metascape platform. (C) The network is visualized using Cytoscape 5, colored by cluster IDs, and nodes sharing the same cluster ID are usually close to each other. (D) The gene–gene interaction network of the top 10 hub genes with the 20 most adjacent genes was analyzed using the GeneMANIA database. Each node represents a gene. The color of the linkage of the nodes represents the linkage between the corresponding genes.

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  Figure 8. Identification of the hub gene between RA, COVID-19, and SAB. (A) Venn diagram of the top 10 hub genes and the SARS-CoV-2 gene set. (B, C) The expression of IFI44, OAS1, IFI44L, ISG15, and HERC5 in the GSE93272 and GSE33341 datasets was analyzed using split-face violin plots. Red indicates the RA group, yellow indicates the S. aureus group, and blue indicates the HC group.

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  Figure 9. Functional enrichment analysis: Metascape and GeneMANIA of five hub genes. (A) Pathway and process richness analysis of the Metascape platform. (B) Summary of enrichment analysis of DisGeNET 13 on Metascape platform. (C) The network is visualized using Cytoscape 5, colored by cluster IDs, and nodes sharing the same cluster ID are usually close to each other. (D) The gene–gene interaction network of the five hub genes with the 20 most adjacent genes was analyzed using the GeneMANIA database. Each node represents a gene. The color of the linkage of the nodes represents the linkage between the corresponding genes.

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  Figure 10. Construction of TF-hub gene and miRNA-hub gene network using NetworkAnalyst. (A, B) TF-hub gene network and simplified diagram. Red circles are genes, and yellow squares are TF. (C, D) miRNA-hub gene network (miRTarBase v8.0) and simplified diagram. (E, F) miRNA-hub gene network (TarBase v8.0) and simplified diagram. Circles are genes, and squares are miRNAs.

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  Figure 11. Screening for key genes. (A, B) Gray dots represent genes not substantially differently expressed in RA and HC groups (P > 0.05), red triangles represent upregulated genes (P < 0.05), and green triangles represent downregulated genes (P < 0.05) in GSE17755 and GSE55235 datasets. (C) Gray dots represent genes not substantially differently expressed in S. aureus and HC groups (P > 0.05), red triangles represent upregulated genes (P < 0.05), and green triangles represent downregulated genes (P < 0.05) in the GSE13670 dataset. (D) The Venn diagram of five hub genes with the three validation sets of DEGs.

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  Figure 12. Validation of key genes. (A–C) The expression of IFI44 in GSE17755, GSE55235, and GSE13670. Red for RA/S. aureus group, and cyan for HC group. (D–F) The AUC of the ROC curve verifies the diagnostic validity of IFI44 in GSE17755, GSE55235, and GSE13670 (P < 0.05).