Extended Data Fig. 7: Gene expression analysis of infected versus bystander single cells.

a. scRNA-seq profiles of epithelial cells from Liao et al.⁴². Cells are colored by assigned epithelial cell type. b. Expression of selected marker genes for each cell type. c. Identification of infected cells using Viral-Track⁶⁷. Any cell with at least one detected high-confidence viral transcript is classified as positive. d. Number of viral RNA positive cells (vRNA+) by cell type. e. As a positive control for our methodology, expression of LY6E, a previously identified antiviral factor and GOF-enriched hit in our screen, is shown in epithelial progenitor cells comparing levels in vRNA+ cells (n = 282) and vRNA- cells (n = 9063). Indicated comparison was made by Mann-Whitney U test. f-g. Comparison of gene expression in viral RNA positive (vRNA+) and viral RNA negative (vRNA-) cells. (f) Viral UMI cutoffs of >65% of all cells were used to identify vRNA+ cells (vRNA + , n = 94 cells and vRNA-, n = 9251 cells). (g) Same as (f) except a viral UMI cutoff of >80% was used. (vRNA + , n = 48 cells, and vRNA- n = 9297 cells). Indicated comparisons were made by Mann-Whitney U test. For all panels: *= p < 0.05, **= p < 0.01, ***= p < 0.001, ****= p < 0.0001. Box plots: Upper and lower hinges correspond to the 75th and 25th percentiles, center line corresponds to the median, and whiskers extend to the most extreme point no further from the closest hinge than 1.5 * the interquartile range.