Table 3.
Enriched functional terms shared among the 35 candidate gene clusters from the integrated network of consensus DEGs of the three SARS-CoV-2 infection models and the SARS-CoV-2-host protein interaction map
| Cluster | Enriched functional terms |
|---|---|
| C-7 and C-29 | atypical NF-κB pathway; autoimmune disease |
| C-2, C-7, and C11 | apoptotic mitochondrial changes; positive regulation of apoptotic process by virus; PAR1-mediated thrombin signaling events; ceramide signaling pathway; abnormal melanocyte morphology; abnormal splenocyte apoptosis; leukocyte count |
| C-8 and C-19 | canonical NF-κB pathway; regulation of cytoplasmic translation |
| C-2, C-7, C-3, and C-25 | genes regulated by NF-κB; circadian rhythm—mammal; genes upregulated in regulatory T (FOXP3+) cells from B6 mice |
| C-18, C-2, and C-5 | proliferating basal; proliferating macrophages; DNA replication; E2F transcription factor network |
| C-13, C-7, and C-2 | OLR1+ classical monocytes; neutrophil activation; β3 integrin cell surface interactions; liver inflammation; increased susceptibility to bacterial infection |
| C-1, C-7, and C-10 | dendritic cells; proliferating macrophages; innate immune response; increased susceptibility to infection; platelet function tests; immune effector process |
| C-2 and C-3 | adventitial fibroblasts; mesothelial; intermediate monocytes; mRNA metabolic process; abnormal heart ventricle morphology; genes upregulated in response to low oxygen levels |
| C-21 | decreased coronary flow rate; abnormal renal vascular resistance; airway wall thickness measurement; orotic acid measurement |
| C-23 and C-35 | plasma cells; peptide metabolic process; translational initiation; regulation of translation; mitochondrial gene expression and translation |
| C-8 and C-2 | apoptosis; activation of innate immune response; NOD-like receptor signaling pathway; Toll-like receptor signaling pathway; TNF receptor signaling pathway; immune system disease; respiratory system disease |
| C-7 | NF-κB signaling; response to cytokine; signal transduction through IL1R; IL23-mediated signaling events; genes related to CD40 signaling; T cell receptor signaling pathway; IL12-mediated signaling; abnormal interleukin secretion; abnormal T cell physiology; mast cell/basophil type 2; cDC1; Langerhans dendritic cells; cDC2; ulcerative colitis; Crohn's disease; inflammatory biomarker measurement; asthma; hypothyroidism; granulocyte count |
| C-9 and C-2 | cell-substrate adhesion; extracellular matrix; genes encoding collagen proteins; endothelial cells; AT1; fibroblasts; smooth muscle cells; myofibroblasts; intracerebral hemorrhage; Marfan syndrome; β-blocking agent use measurement |
| C-10 and C-2 | genes encoding extracellular matrix; arterial vascular endothelial cells; smooth muscle cells; platelet degranulation; membrane fusion; vesicle fusion; VEGF and VEGFR signaling network |
| C-5, C-12, and C-28 | mitochondrion organization; mitochondrion transport; oxidative phosphorylation; ATP biosynthesis; abnormal mitochondrial crista morphology; Alzheimer's; Parkinson's |
| C-16 and C-17 | fatty acid catabolic process; peroxisome organization; lipid oxidation; propanoate metabolism; PPAR signaling pathway; abnormal lipid level; blood metabolite measurement |
The shared terms (biological processes, pathways, cell types, and phenotypic traits) are found through meta-analysis of the enriched terms from different annotation categories for the 35 gene clusters. The complete network along with all enriched terms and cluster details are presented in Table S10. IL, interleukin; cDC1 and cDC2, conventional dendritic cell types 1 and 2; PPAR, peroxisome proliferator-activated receptor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.