Fig. 2: Global Alu editing across living and postmortem DLPFC.

A Alu editing index (AEI; y axis) computed on bulk RNA-seq from living and postmortem (PM) DLPFC. Two-sided linear regression was used to test for significance. B ADAR, ADARB1, and ADARB2 normalized expression profiles on bulk including RNA-seq between living and PM. All boxplots show the medians (horizontal lines), upper and lower quartiles (inner box edges), and 1.5× the interquartile range (whiskers). Reported BH adjusted p values were derived from a moderated t test comparing transcriptome-wide gene expression between living and postmortem tissue. C Linear mixed model explaining AEI variance by eleven known biological and technical factors. D UMAP dimension reduction analysis of snRNA-seq classified nine unique cell populations. Values in brackets indicate the number of cells per sub-population: excitatory (EXC) and inhibitory (INT) neurons, astrocytes (AST), microglia (MG), oligodendrocytes (OLI), OLI precursor cells (OPCs), endothelial cells (ENDO). E The mean frequencies for each cell population quantified between living and PM. Two-sided linear regression was used to test for significance. (F) Hierarchical clustering of scaled ADAR, ADARB1, and ADARB2 expression across all cell populations. G Cell type-specific ADAR, ADARB1, and ADARB2 expression for living and PM. H Alu editing index computed for each cell population for each donor and compared across living and PM samples (bottom). PM-induced effect sizes calculated by Cohen’s d for each cell population (top). G, H Two-sided linear regression was used to test for significance (^*denotes p < 0.05). All boxplots show the medians (horizontal lines), upper and lower quartiles (inner box edges), and 1.5× the interquartile range (whiskers). Two-sided linear regression was used to test for significance. I Pearson’s correlation coefficient between the mean Alu editing index and mean normalized ADARB1 expression for each cell population according to living and PM samples. Standard error bars capture group-wise variance within living and postmortem tissues, respectively. RNA-seq analysis encompassed 164 and 233 biologically independent samples from living and postmortem sources, respectively. Single-nucleus RNA-seq was conducted on 31 living and 21 PM biologically independent samples. All boxplots in this figure show the medians (horizontal lines), upper and lower quartiles (inner box edges), and 1.5 × the interquartile range (whiskers).