Extended Data Fig. 2: Anti-IFNAR2 and Remdesivir therapy reverses infection induced transcriptional changes (matched to figure 1).
From: Inflammasome activation in infected macrophages drives COVID-19 pathology
a. Similarity comparison of uninfected, infected, and therapeutically manipulated lungs based on dexamethasone suppressed genes. Pearson correlation. Duplicates analysed for each condition. b. Genes suppressed by both dexamethasone and combined therapy of Remdesivir and anti-IFNAR2 (log2, foldchange < −1, P adj < 0.05). P adj: For the adjusted P values the Bonferroni correction was used. Duplicates analysed for each condition. Dexamethasone suppressed genes significantly overlapped with genes significantly suppressed by combined anti-IFNAR2 and Remdesivir therapy (64% overlap). See Supplementary Table 1 for a full list of genes and their normalized expression. c. Network analysis (STRING v11.0) of genes suppressed by both dexamethasone and combined therapy of Remdesivir and anti-IFNAR2 (as shown in Extended Data Fig. 2b). Duplicates analysed for each condition. K- means clustering (n = 4). d. Pathway (Ingenuity) analysis of genes suppressed by both dexamethasone and combined therapy of Remdesivir and anti-IFNAR2 (as shown in Extended Data Fig. 2b). Duplicates analysed for each condition. Fisher's Exact Test was used to determine statistical significance in the overlap between the dataset genes and the genes suppressed by therapy. e. Transcriptional landscape of human immune cells at single cell level in uninfected or infected (28 d.p.i.). MISTRG6-hACE2 mice. Cluster identifying genes comparing human immune cells from infected (28 d.p.i.) or uninfected lungs for 17 clusters shown in Fig. 1e. Marker genes for each cluster of cells were identified using the Wilcoxon rank-sum test with Seurat. Pooled duplicates analysed for each condition.
