In addition to the TF-gene relationships, we assessed the state of DNA damage in OUD using two published gene signatures of DNA damage13. The neuronal DNA damage signatures were collected by Welch et al. from fluorescence activated sorting of mouse brain nuclei gated for NeuN + :gH2AX+ nuclei. Using the human orthologs of these mouse genes, we scored our single nuclei RNA-seq datasets with the AUCell method to study the differences in DNA damage gene signatures between unaffected and OUD individuals or no-morphine or chronic morphine treated rhesus macaques. We applied the same pseudobulk average of DNA damage scores and reported the linear regression interaction between OUD and cell type in DNA damage signatures in Supplementary Data 1–S10. We similarly applied the same pseudobulk average of DNA damage scores and report the linear regression interaction between chronic morphine exposure and cell type regressing out the match pair in DNA damage signatures.
