Patients with dermatomyositis shared partially similar transcriptome signature with COVID-19 infection

Figures & data

Table 1. Basic information of the two microarrays.

	Subjects	Platform	Organization name	Country	Submission date/updated date	Number of samples (patients/NC)	Reference
GSE46239	The skin of active rashes of DM patients.	GPL570	Medimmune LLC	USA	2013.4.20/2020.12.09	48/4
GSE193068	COVID-19 skin lesions	GPL31171	CHUV	Switzerland	2022.1.05/2022.3.17	10/4	[17]

Figure 1. Volcano plots of datasets. (A) Volcano plots of GSE46239 in DM. The ordinate represents log2 (fold change), the abscissa represents log10 (p value), each point represents a gene, |log2 FC| ≥1and p < 0.05 as thresholds. (B) Volcano plots of GSE193068 in COVID-19. (C) The intersection of the two data sets. (D) KEGG pathway of these common genes.

Figure 2. Gene ontology analysis and significantly enriched signal pathway of differentially expressed genes (DEGs) in DM. A. BP analysis of DEGs. B. MF analysis of DEGs. C.CC analysis of DEGs. D.KEGG analysis of DEGs.

Figure 3. Protein–protein interaction (PPI) network of differentially expressed genes (DEGs) in DM. A. Based on the STRING online database, 173 genes were filtered into the DEG PPI network. B. The most significant module 1 (25 genes) from the PPI network. C. The most significant module 2 (23 genes) from the PPI network.

Figure 4. Functional and Pathway Enrichment of Module Genes. A. BP analysis of Module Genes. B. MF analysis of Module Genes. C.CC analysis of Module Genes. D.KEGG analysis of Module Genes.

Figure 5. Hub gene and KEGG pathway analysis in DM. A. Top 10 hub genes with highest MCC score in cytoHubba. B. KEGG pathway analysis of hub genes.

Table 2. 380 DEGs were identified in GSE46239, including 271 up-regulated genes and 109 down-regulated genes.

DEGs	Gene name
Up-regulated	STEAP4, FAM46A, IFI6, IFITM1, LOC101928916, ERG, ADGRL4, CNN3, IFITM2, ANGPT2, SEMA3C, COL6A1 , IFI44L, ADAMTS1, GIMAP6, IFIT3, FAM162B, ISG15, CMPK2, GIMAP7, SIGLEC1, RSAD2, MX1, IFI44, EPSTI1, IFIT1, CYBB, SERPING1, BST2, FAM198B, IFITM3, NRP2, HERC5, GIMAP4, C1QC, PLSCR1, IFI27, GIMAP8, FLI1, NT5E, TFPI, C1QA, C1R, ADAMTS5, SEC24D, THBS1, PRRX1, TM4SF18, MX2, LY96, LY6E, DDX60L, IFIT5, IFITM2, ADM, LAP3, CD163, LOC101930489, SAMHD1, TNFAIP6, CFI, OAS2, CTHRC1, LGALS3BP, STAT1, MDK, SRGN, NID1, SLC15A3, EIF2AK2, SP110, DDX58, FGF7, C1S, OASL, HERC6, EGFL6, VCAN, SP140L, MAF, IGF1, TLR4, STARD4, IFIT2, OAS3, TRIM5, IRF9, IFI16, CP, XAF1, C1QB, SP100, TNFSF13B, APOL6, THEMIS2, RNASE1, MCTP1, GREM1, TRIM22, ACKR4, LGALS9, LUM, BLZF1, STAT2, RSPO3, SAMD9, USP18, MS4A7, NDC80, CCL8, LAIR1, IKBIP, MS4A4A, C3AR1, ICAM2, CCR1, NR2F2, ANGPTL1, APOL3, APOL2,PARP9, SOCS1, EMILIN2, TNFSF10, ISG20, CARD8-AS1, GBP3, DDX60, CLIC2, TAP2, MS4A6A, VGLL3, CYR61, PARP14, CFB, MICB, IFIH1, APOBEC3G, ADAMDEC1, TFEC, HELZ2, C19orf66, GIMAP2, SAMD9L, NCEH1, RARRES3, SLFN12, THY1, PTN, ST8SIA4, CASP1, DTX3L, NEXN, CXCL10, MMRN1, CLEC7A, GBP1, IFI35, CXCR4, IGFBP6, FCGR1, AVPR1A, SOCS3, CTGF, SNX10, AIM2, RNF213, PNPT1, OAS1, CXCL2, IRF7, UBE2L6, CTSS, PLA1A, SLFN5, SPOCK1, FCGR1B, C1orf162, CXCL11, GBP5, BATF2, RTP4, ICAM1, ITGA4, KYNU, IRF8, APOBEC3, SLC44A5, DKK1, CCL5, SLC2A3, GNLY, TMEM100, GSTT2, PCOLCE2, SULF1, PRH1-PRR4, HAVCR2, PARP12, FAM26F, ODF3B, NMI, DPP4, PLAC8, CARD16, VSIG4, GALNT15, ZBP1, KLHDC7B, TYMP, TAGAP, LYN, PSMB9, LILRB2, VCAM1, TLR3, CD36, CCL2, MMP9, CH25H, WARS, SERPINA1, TDO2, APOBEC3A, GBP4, FCER1G, MIR21, APOL1, LCP2, GPR183, KLRC, ZC3HAV1, SERPINE1, BTN3A3, 1-Mar, IFI3, IDO1, NKG7, IGSF6, MT1M, LIPA, IL18BP, MFAP5, XCL, TIMD4, GZMB, ERAP2, MPZL2, PLA2G2A, CXCL9, XCL1, XIST, SELE, FPR3, SAMSN1, RGS1, CCL3,CD86, ADORA3, CCR7, BCL2A1, IGFL1, LAMP3, ZNF595, CD274, CD69, SELL, SAA2, SLAMF7, SPP1, PTPRC
Down-regulated	WNT4, BRWD3, KMT2A, TLCD2, LYST, HECTD1, SPPL3, SDHAP2, CHD4, KANSL1, FTX, LOC158863, GNAL, GPR158, COL6A5, SLC1A2, FRMD4A, LRRC37A3, FGFR2, ADGRG6, LINC01550, LOC101930303, KIT, MYB, DPP6, CLN8, MIR205HG, MYH10, TAPT1-AS1, NFYA, MAB21L3, BAGE2, SF1, HERC1, MIR181A2HG, CD99P1, LOC101928524, PDXDC1, ABHD5, POU2F3, CD1E, WNT2B, TRPM1, PLP1, C11orf80, DDX6, XG, LOC729732, NHLH2, ABCA5, ITGB8, ZDHHC11, ALDH3A1, LOC389834, DCT, MAGI1, CXCL14, FOXQ1, GUSBP1, PCSK2, IPO5P1, ALDH3A2, SOX6, FCGBP, ARHGEF28, PAIP2B, CDHR1, TPPP, TFAP2B, SMAD5-AS1, PDE6A, SLC47A1, BPY2, MTURN, CD1A, CNTN1, APOE, ZNF254, SLC14A1, CD1C, CD207, LOC101930123///EEF2K, CHP2, MLANA, PON3, MUC1, GPLD1, GABPB1-AS1, KDM5D, AGPAT3, AATBC, OLAH, RPS4Y1, USP9Y, ACSBG1, TMEM97, TYR, TTTY14, EIF1AY, CRAT, SLC27A6, DDX3Y, FADS1, TXLNGY, HLA-DQA1, TF, GAL, FCER1A,CNTNAP3

Table 3. Functional roles of top 10 hub genes with highest MCC score.

No.	Gene symbol	Full name	MCC score	Function
1	MX1	MX dynamin like GTPase 1	2.25E + 21	Interferon-induced dynamin-like GTPase participating in the cellular antiviral response.
2	ISG15	ISG15 ubiquitin-like modifier	2.25E + 21	Chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections.
3	IFIT3	interferon induced protein with tetratricopeptide repeats 3	2.25E + 21	Inhibiting cellular as well as viral processes, cell migration, proliferation, signaling, and viral. Negatively regulates the apoptotic effects of IFIT2.
4	IFIT1	interferon induced protein with tetratricopeptide repeats 1	2.25E + 21	Inhibiting the expression of viral messenger RNAs.
5	RSAD2	radical S-adenosyl methionine domain containing 2	2.25E + 21	Inhibiting viral replication and translational initiation.
6	IFIT2	interferon induced protein with tetratricopeptide repeats 2	2.25E + 21	Inhibiting expression of viral messenger RNAs and promoting apoptosis.
7	IFI6	interferon alpha inducible protein 6	2.25E + 21	Induced by interferon, playing a critical role in the regulation of apoptosis.
8	XAF1	XIAP associated factor 1	2.25E + 21	A negative regulator of members of the IAP that inhibits anti-caspase activity of BIRC4.
9	IRF9	interferon regulatory factor 9	2.25E + 21	Virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity.
10	MX2	MX dynamin like GTPase 2	2.25E + 21	Interferon-induced dynamin-like GTPase with potent antiviral activity against HIV-1.

Figure 6. Hub gene expression in the muscle tissue. (IIM, idiopathic inflammatory myopathy, n = 24; NC, normal control, n = 12. **p < 0.005; ***p < 0.001; ****p < 0.0001).

Figure 7. RSAD2 is elevated in skin fibroblasts of patients with DM. (A:Representative immunohistological staining of RSAD2 in the skin of DM and NC patients. B. Statistical analysis of RSAD2 immunohistochemistry. DM, dermatomyositis, n = 3; NC, normal control, n = 3. Scale bar = 50 μm.).

Domizio JD, Gulen MF, Saidoune F, et al. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature. 2022;603(7899):145–151.

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Data availability

The data used to support the findings of this study is available from GSE46239 and GSE193068.