Several limitations of our resource stem from challenges of profiling single cell transcriptomes in postmortem human brains. While the nuclear transcriptome correlates on whole with the transcriptomes of other subcellular compartments, there are notable differences in mRNA trafficking within certain neural cell types and synapses. Furthermore, the nuclear transcriptome does not capture post-transcriptional regulation. Further, the sex-biased differential expression in OUD is likely influenced by cultural and behavioral factors that are confounded with biological sex. Lastly, while this resource will be useful to identify the consequences of OUD in the postmortem brain transcriptome, integration of our findings with other types of approaches from genetics to functional genomics in clinical cohorts to animal models of opioid addiction could contribute to a greater understanding of opioid addiction and aid in the realization of treatment strategies.
