SARS-CoV-2 infection transmits worldwide and its mortality rate has increased in recent years. This research represents the first complete study of a genes linked with SARS-CoV-2 virus infection, using bioinformatics analysis. However, the molecular mechanisms of SARS-CoV-2 infection remain poorly understood. Thus, probable biomarkers for diagnosis and treatment with high competence are crucially demanded. Microarray technology has been proved to be a needful approach to diagnose novel biomarkers in SARS-CoV-2 infection.
In the current investigation, expression profiling by high throughput sequencing dataset was analyzed to obtain DEGs between SARS-CoV-2 infections samples and mock samples. A total of 928 DEGs were identified, including 461 up regulated genes and 467 down regulated genes. Genes such as SOCS3 [47] and IL1A [48] were liable for progression of influenza virus infection, but these genes may be linked with progression of SARS-CoV-2 infection. Genes such as KLF6 [49], DUSP1 [50] and OLFM4 [51] were associated with development of respiratory syncytial virus infection, but these genes may be responsible for advancement of SARS-CoV-2 infection. IL6 was involved in progression of SARS-CoV-2 infection [52]. Genes such as MAGT1 [53], CD24 [54] and UGT1A7 [55] were involved in progression of various viral infections, but these genes may be associated with development of SARS-CoV-2 infection. AQP1 was linked with development of porcine reproductive and respiratory syndrome virus infection [56], but this gene may be responsible for progression of SARS-CoV-2 infection.
In the pathway enrichment analysis, many up and down regulated genes may play a very key role in progression of SARS-CoV-2 infection. Enriched genes such as CXCL9 [57], CX3CL1 [58], IFNB1 [59], IL7 [60], TNFSF10 [61], IFNL3 [62], EGR1 [63], USP18 [64], DDX58 [65], UBA7 [66], IFI35 [67], IFIT2 [68], IFIT1 [69], TRIM5 [70], RSAD2 [71], XAF1 [72], MX2 [73], GBP1 [74], TRIM21 [75], FGF19 [76], PELI1 [77], OAS1 [78], DUSP10 [79], TLR6 [80], TICAM1 [81], DDC (dopa decarboxylase) [82], UGT1A1 [83], STMN1 [84], CYP27A1 [85] and ACE (angiotensin I converting enzyme) [86] were linked with advancement of various viral infections, but these genes may responsible for progression of SARS-CoV-2 infection. Enriched genes such as CCL2 [87], FLT3 [88], CXCL8 [89], IL11 [90], CXCL10 [91], TNF (tumor necrosis factor) [92], EGR2 [93], TRIM22 [94], PML (promyelocyticleukemia) [95], ICAM1 [96], IFITM1 [97], IFITM2 [98], ISG15 [99], SOCS1 [100], IRF1 [101], IRF7 [102], ISG20 [103], STAT2 [104], OAS2 [105], HERC5 [106] and TNFAIP3 [107] were associated with advancement of influenza virus infection, but these genes may be liable for development of SARS-CoV-2 infection. . Enriched genes such as CCL20 [108], TSLP (thymic stromal lymphopoietin) [109], IL7R [110], IFIT3 [111] and OASL (2'-5'-oligoadenylate synthetase like) [112] were involved in the development of respiratory syncytial virus infection, but these genes may be associated with development of SARS-CoV-2 infection. SAMHD1 was involved in progression of porcine reproductive and respiratory syndrome virus infection [113], but this gene may be liable for progression of SARS-CoV-2 infection. Enriched genes such as JAK2 [114] and ACE2 [115] were responsible for progression of SARS-CoV-2 infection. As given in the pathway enrichment analysis for up and down regulated genes, HSD17B3, CYP21A2, TNFRSF4, CXCL11, FLT3LG, CSF2, TNFSF13B, IL12A, IL15RA, INHBA (inhibin subunit beta A), IL17C, IL22RA1, BMP2, CXCL2, CXCL3, LTB (lymphotoxin beta), IFNL2, IFNL1, FOS (Fos proto-oncogene, AP-1 transcription factor subunit), GATA3, PTGS2, JUN (Jun proto-oncogene, AP-1 transcription factor subunit), EGR3, EGR4, UBE2L6, HLA-F, SPTBN5, RASGRP3, TRIM38, KLB (klotho beta), MAP3K8, MT2A, PSMB9, FGF18, DUSP8, RELB (RELB proto-oncogene, NF-kB subunit), LGALS9, RASGRP1, FST (follistatin), WIF1, NFKBIA (NFKB inhibitor alpha), PNMT (phenylethanolamine N-methyltransferase), ALDH2, UGT1A10, UGT1A8, UGT1A6, UGT1A5, UGT1A9, UGT1A4, UGT1A3, UGT2A3, SNTA1, EPHX1, ADH6, FDX1, ACSS1, GSTO2, GGT1, NR1H4, GLYATL2, GSTA4, CYP2U1, CYP4F3, HADHB (hydroxyacyl-CoA dehydrogenase trifunctionalmultienzyme complex subunit beta), AGT (angiotensinogen), MME (membrane metalloendopeptidase), PPT1 and PRDX3 are novel biomarkers for SARS-CoV-2 infection.
Similarly, GO enrichment analysis, many up and down regulated genes may play a very key role in progression of SARS-CoV-2 infection. Enriched genes such as IFNL4 [116], ZFP36 [117], CD274 [118], MIR21 [119], CYP1A1 [120], CMPK2 [121], C4A [122], SERPINE1 [123], CCRL2 [124], CD69 [125], FAH (fumarylacetoacetate hydrolase) [126], ERFE (erythroferrone) [127], SERINC5 [128], ADI1 [129], AP2M1 [130], PRIMPOL (primase and DNA directed polymerase) [131], BIRC5 [132] and TF (transferrin) [133] were responsible for advancement of various viral infections, but these genes may be involved in progression of SARS-CoV-2 infection. Enriched genes such as APOBEC3G [134], NLRC5 [135], PTX3 [136], FAP (fibroblast activation protein alpha) [137] and CAT (catalase) [138] were linked with development of influenza viral infection, but these genes may be associated with progression of SARS-CoV-2 infection. Enriched genes such as IFI16 [139], TAP1 [140] and PIN1 [141] were involved in development of porcine reproductive and respiratory syndrome virus infection, but these genes may be associated with progression of SARS-CoV-2 infection. NLRP3 was key for advancement of SARS-CoV-2 infection [142]. PDK1 was liable for development of SARS corona virus infection [143], but this gene may belinked with advancement of SARS-CoV-2 infection. As given in the GO enrichment analysis for up and down regulated genes, PDE2A, PDE4B, NT5C3A, PGLYRP2, DTX3L, PLAC8, NOCT (nocturnin), PMAIP1, ZC3H12A, DHX58, TENT5A, IFI44, BATF2, TXNIP (thioredoxin interacting protein), SH2D1B, MIR181B1, RAET1L, STX11, ZC3HAV1, CYLD (CYLD lysine 63 deubiquitinase), TAGAP (T cell activation RhoGTPase activating protein), BCL3, PTGER4, RTP4, GFI1, IFIH1, CLEC4A, GLI2, C4B, GPER1, CRTAM (cytotoxic and regulatory T cell molecule), PCK1, acetylcholinesterase (Cartwright blood group), TRPC4, DSCAML1, HEG1, PLAUR (plasminogen activator, urokinase receptor), SLITRK6, ACKR4, LAYN (layilin), GRIA2, MMP25, EPHA4, SECTM1, VSTM1, RIMKLA (ribosomal modification protein rimK like family member A), ACO1, ETFB (electron transfer flavoprotein subunit beta), ETFDH (electron transfer flavoprotein dehydrogenase), MDH1, HNMT (histamine N-methyltransferase), PGK1, FABP6, ACSM3, FBP1, HOGA1, SCP2, ECI2, ALDH6A1, PCYOX1, MPC2, HACD3, FOLR1, SHMT1, ACSF2, SLC3A1, CRYM (crystallin mu), CSPG5, PPA2, AKR1C3, DHFRP1, SPR (sepiapterinreductase), BDH2, GATM (glycine amidinotransferase), BCKDHB (branched chain keto acid dehydrogenase E1 subunit beta), PSMD10, ITIH2, PHGDH (phosphoglycerate dehydrogenase), BTD (biotinidase), SLC25A21, OAT (ornithine aminotransferase), OAZ1, HACD2, ECH1, BCO2, BNIPL (BCL2 interacting protein like), PAH (phenylalanine hydroxylase), LTC4S, DSEL (dermatansulfateepimerase like), ATPSCKMT (ATP synthase c subunit lysine N-methyltransferase), COX16, ACYP2, TRMT2B, TSTD1, ASB9, UCP2, AK4, CEBPZOS (CEBPZ opposite strand), SERHL2, HSPE1, SLC25A27, COA3, AGR2, MACROD1, COX11, NUBPL (nucleotide binding protein like), CRLS1, BRI3BP, DNLZ (DNL-type zinc finger), CYBA (cytochrome b-245 alpha chain), KLK6, NDUFS7, PSAP (prosaposin), NDUFAF8, ACOT13, SRI (sorcin), TOMM20, NDUFA2, SGPP1, TMEM160, HEBP1, AKR1B10, DPYSL2, ATP5IF1, NRGN (neurogranin), DTYMK (deoxythymidylate kinase), NTHL1, PRDX2, TMBIM6, GSR (glutathione-disulfidereductase), TFRC (transferrin receptor), ANXA10, SAMD13, FAHD1, ENDOG (endonuclease G), COX14, FMO5, CRYZ (crystallin zeta), ACBD7, KCNAB1, CREG2 and TCN1 are novel biomarkers for SARS-CoV-2 infection.
PPI network was constructed and modules extracted to explore the molecular mechanism SARS-CoV-2 infection. In this investigation, the expression of hub genes in SARS-CoV-2 infection. Hub gene CH25H was liable for progression of porcine reproductive and respiratory syndrome virus infection [144], but this gene may be involved in advancement of SARS-CoV-2 infection. Hub genes such as TRAF1 [145], IFIT5 [146], CFTR (CF transmembrane conductance regulator) [147] and SMARCA2 [148] were key for progression of influenza viral infection, but these genes may be linked with progression of SARS-CoV-2 infection. Hub gene SAP30 was responsible for adavancement of Rift Valley fever virus infection [149], but this gene may be key for advancement of SARS-CoV-2 infection. Hub gene APOE (apolipoprotein E) was responsible for development of SARS-CoV-2 infection [150]. As given in the PPI network and module analysis for up and down regulated genes, FBXO6, ADRB2, SYNPR (synaptoporin), LSMEM1, ARRDC3, ACTA1, LMO2, ATF3, KLF4, PCLAF (PCNA clamp associated factor), TUBA1A, AURKA (aurora kinase A), ARRB1, KPNA2, GALM (galactosemutarotase), HSD17B2, CEACAM7, SEMA3E, EPN3, ROM1, SORL1 and PDCD4 are novel biomarkers for SARS-CoV-2 infection.
Target gene - miRNA regulatory network and target gene - TF regulatory network analysis (up and down regulated genes) can be regarded as key to the understanding of SARS-CoV-2 infection and might also lead to new therapeutic approaches. Hub genes such as PROX1 [151] and HOXA13 [152] were responsible for development of hepatitis B virus infection, but these genes may be essential for advancement of for SARS-CoV-2 infection. As given in the target gene - miRNA regulatory network and target gene - TF regulatory network for up and down regulated genes, APOL6, CHAC1, KLF2, CPM (carboxypeptidase M), CFI (complement factor I) and PGP (phosphoglycolate phosphatase) are novel biomarkers for SARS-CoV-2 infection.