Fig. 2: Cellular composition affects the transcriptional responses to viral stimuli.
From: Dissecting human population variation in single-cell responses to SARS-CoV-2
a, Cell type proportions within each immune lineage in Africans (AFB) and Europeans (EUB). brt, bright. b, The number of genes differentially expressed between the African and European groups in the basal state (NS) or in response to SARS-CoV-2 (COV) or IAV, in each immune lineage. Numbers are provided before and after adjustment for cellular composition. c, Examples of popDRGs, either shared across cell types and viruses (GBP7) or specific to SARS-CoV-2-stimulated myeloid cells (CCL23). Statistical analysis was performed using two-sided Student’s t-tests with adjustment using the Benjamini–Hochberg method; *P < 0.001. Exact P values are provided in Supplementary Table 4b. d, The effect of adjusting for cellular composition on genes differentially expressed between populations after exposure to SARS-CoV-2. Adjustment reduces raw population fold-changes (FCa versus FCr) in the expression of genes that are differentially expressed between memory-like NK cells and CD56dim NK cells (red triangles; genes with similar expression are shown in grey). e, The effect of adjusting for cellular composition on population differences in the response to viral stimulation for genes involved in the positive regulation of cell migration (GO:0030335) in the NK lineage. For each stimulus, gene set enrichment analysis enrichment curves are shown before and after adjusting on the basis of cellular composition. Grey shades indicate the 95% expected range for the enrichment curve when gene labels are permuted at random. f, The distribution of CD8+ EMRA T and memory-like NK cell frequencies in Africans and Europeans according to CMV+/− serostatus. P values (P < 0.01) calculated using Wilcoxon’s two-sided rank-sum tests are shown. For c and f, the centre line shows the median; the notches show the 95% confidence intervals (CIs) of the median; the box limits show the upper and lower quartiles; and the whiskers show 1.5× interquartile range. The number (n) of independent biological samples is indicated where relevant.
