Extended Data Fig. 9: Age, sex, and smoking status associations with expression of ACE2, TMPRSS2, and CTSL across level 3 cell type annotations modeled without interaction terms.

a, Age, sex, and smoking assocations with expression of ACE2 (blue), TMPRSS2 (yellow), and CTSL (green) modeled without interaction terms on 985,420 cells from 164 donors. Level 3 cell types are shown on the y-axes, and are subdivided by level 1 cell type annotations (top to bottom: epithelial, endothelial, stromal and immune cells). The effect size (x axis) is given as a log fold change (sex, smoking status) or the slope of log expression per year (age). Positive effect sizes indicate increases with age, in males, and in smokers. As the age effect size is given per year, it is not directly comparable to the sex and smoking status effect sizes. Colored bars: associations with an FDR-corrected p-value<0.05 (one-sided Wald test on regression model coefficients), consistent effect direction in pseudo-bulk analysis, and consistent results using the model with interaction terms (Methods). White bars: associations that do not pass all of the three above-mentioned evaluation criteria. Error bars: standard errors around coefficient estimates. Error bars are only shown for colored bars (indications or robust trends) to limit figure size. Only cell types with at least 1000 cells across donors are included. Number of cells and donors per cell type: Basal: 155877, 105, Multiciliated lineage: 37530, 157, Secretory: 22306, 140, Rare: 2676, 71, Submucosal secretory: 33661, 45, AT1: 29973, 101, AT2: 155512, 104, Arterial: 3497, 37, Capillary: 15745, 34, Venous: 7173, 33, Lymphatic EC: 5055, 76, Fibroblasts: 9112, 51, Airway smooth muscle: 1077, 13, B cell lineage: 11761, 90, T cell lineage: 52139, 97, Innate lymphoid cells: 29836, 56, Dendritic cells: 9017, 90, Macrophages: 156964, 89, Monocytes: 42703, 96, Mast cells: 13581 cells, 88 donors. b, Robustness of associations to holding out a dataset. The values show the number of held-out datasets that result in loss of association between a given covariate (rows) and ACE2, TMPRSS2, or CTSL expression in a given cell type (columns). Robust trends are determined by significant effects that are robust to holding out any dataset (0 values). From left to right: results for ACE2, TMPRSS2, and CTSL. AT1, 2: alveolar type 1, 2. EC: endothelial cell.