Extended Data Fig. 3: Extended analysis of transcriptional profiles and immune cell infiltration in APOE knock-in mice during COVID-19.
From: Common human genetic variants of APOE impact murine COVID-19 mortality
a, Module eigengenes averaged per condition. b, Independent validation of correlation of specific gene modules with APOE genotype in lungs of male APOE knock-in mice on day 4 post infection with SARS-CoV-2 MA10. Red indicates positive correlation of module eigengenes with APOE genotype ordered by its impact on COVID-19 survival (E3 > E2 > E4); stars indicate significant correlations (one-sided Pearson correlation tests). c, Averaged module eigengenes in the validation experiment. d, Correlation of gene modules with APOE genotype in lungs of 7-weeks old female APOE knock-in mice on day 4 post infection. Red indicates positive correlation of module eigengenes with APOE genotype ordered by its impact on COVID-19 survival (E3 > E2 > E4); stars indicate significant correlations (one-sided Pearson correlation tests). e, Averaged module eigengenes of modules significantly associated with APOE genotype in mice from (d). f–g, Network plot of the top ten hubgenes (genes with highest intramodular connectivity) (f) and the top five GO pathways enriched in the 348 genes of the black module (g) (P values according to hypergeometric tests adjusted for FDR). h, Expression of genes constituting the midnightblue and greenyellow modules. Hubgenes are annotated by name. i–o, Network plots of the top ten hubgenes (I,k,m,o) and the top five GO pathways enriched in 45, 67, and 58 genes of the greenyellow, midnightblue, and yellow modules, respectively (j,l,n) (P values in j, l, and n according to hypergeometric tests adjusted for FDR). No pathways were enriched in the 24 genes making up the pink module. p, Immunofluorescence staining for CD45+ cells in lungs of APOE knock-in mice on day 4 post infection (n = 10, 15, 10 for APOE2, APOE3, and APOE4, respectively; P values according to two-sided Mann Whitney tests; .interquartile ranges of the hinges, and box centre and hinges indicate median and first and third quartiles, respectively). Images on the right show representative sections; scale bar, 100 µm.
