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Fig. 4 | Genome Medicine

Fig. 4

From: Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19

Fig. 4

Gene regulatory network (GRN) analysis revealed transcription factors (TFs) driving transcriptomic dysregulation in COVID-19 patients. A TF module scores in PFC microglia. The shade of a violin indicates the median activity score of each individual. Four upregulated TF modules (IRF8, ATF5, SPI1, TAL1) are shown. B Upregulated TF modules in PFC microglia. Colored nodes show the transcription factors (blue, green, brown, and purple), DEGs (red), and a genetically associated gene based on genome-wide association studies (GWAS) (yellow). Nodes without circles are genes regulated by the transcription factors but are not DEGs. The regulatory network is trimmed to show only 14 DEGs, ranked by P-values, and 10 non-DEG genes regulated by each transcription factor. C Enrichment of the GWAS-associated genes in 4 microglia regulons: IRF8, ATF5, SPI1, and TAL1. Circles show odds ratios for the overlap of nominally significant GWAS gene (n = 285 and 560 for blood and brain, respectively, P ≤ 0.05), imputed from a GWAS comparing hospitalized COVID with respect to the general population, and genes of 4 microglia regulons. Error bars show 95% confidence intervals of estimated odds ratios. “Up” are those that are predicted to be upregulated (n = 140 and 297 for blood and brain, respectively, P ≤ 0.05) and “Down” are those that are predicted to be downregulated (n = 145 and 263 for blood and brain respectively, P ≤ 0.05). Analysis is limited to protein-coding genes only. Significant enrichments (P ≤ 0.05, Fisher’s exact test) are denoted by “*”

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