For each individual, we found the mean expression of each gene with nonzero counts. The mean was calculated from the log2 single cell UMI counts normalized to the median count for each cell. To measure inter-individual variability, we then calculated the variance of the mean expression across all individuals. Lin’s concordance correlation coefficient was used to compare the agreement of observed data and synthetic replicates. Synthetic replicates were generated by sampling without replacement either from all cells or cells matched for cell type proportion. Cell type-specific variability estimated as the correlation between synthetic replicates was compared to variability estimates from 23 biological replicates of bulk IFN-stimulated monocyte-derived dendritic cells. Protein coding genes (407/414) originally measured using Nanostring (a hybridization based PCR-free quantification method) were assessed, and variability in the bulk dataset was estimated as repeatability using a linear mixed model56,26.
