Fig. 3: Dynamically regulated A-to-I sites between living and postmortem DLPFC.

A Principal component analysis of editing levels for 54,825 high-confidence sites detected across all samples in the current study. B Differential editing analysis compare delta editing levels (%; x axis) and strength of significance (−log₁₀ adjusted P, y axis) for each site between living and postmortem (PM) DLPFC. Sites are colored by novelty (i.e., detection in REDIportal) and shaped uniquely by genic region. Reported BH adjusted p values were derived from a moderated t test comparing transcriptome-wide A-to-I editing levels between living and postmortem tissue. C Frequency distribution of mean editing levels in living DLPFC (x axis) based on PM biased sites (y axis). D The fraction of genic regions for all living biased and PM biased sites. E Frequency distributions of Pearson’s correlation coefficients (x axis) between the expression for ADAR, ADARB1, ADARB2 relative to editing levels for 54,825 sites. An additional analysis modeled ADAR + ADARB1-ADARB2 to capture ADAR and ADARB1 effects. The total number of sites with significant correlations are listed in the top right corner of each histogram. F Dynamic recoding sites: 27 living-biased recoding sites and 31 postmortem-biased recoding sites ordered by their effect size differences (y axis, lower) and plotted alongside with the mean editing levels (y axis middle). The strength of evolutionary conservation (phastCons) was measured for each site and the probability of being loss of function intolerant (pLI) was measured for each gene (top). G Frequency distributions demonstrating that living biased recoding sites are often more strongly evolutionarily conserved and map to genes with higher pLI relative to PM biased recoding sites. Mann Whitney U test was used to test for significance. Living Brain Project data encompassed 164 and 233 biologically independent samples from living and postmortem sources, respectively.