For human samples, linear regressions of differential AUCell modules, or other quality control metrics at the pseudobulk analyses were performed across biospecimens (N = 22 biospecimens) controlling for relevant covariates including brain region extracting the interaction between OUD diagnosis with cell type. The general linear model for this linear regression for sample level is\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \sim {{{{{\rm{Dx}}}}}}+{{{{{\rm{Age}}}}}}+{{{{{\rm{PMI}}}}}}+{{{{{\rm{RIN}}}}}}+{{{{{\rm{Sex}}}}}}\; {{{{{\rm{and}}}}}}\; {{{{{\rm{for}}}}}}\; {{{{{\rm{cell}}}}}}\; {{{{{\rm{type}}}}}}\; {{{{{\rm{level}}}}}}\; {{{{{\rm{is}}}}}} \\ \sim {{{{{\rm{Dx}}}}}}:{{{{{\rm{Celltype}}}}}}+{{{{{\rm{Celltype}}}}}}+{{{{{\rm{Age}}}}}}+{{{{{\rm{PMI}}}}}}+{{{{{\rm{RIN}}}}}}$$\end{document}~Dx+Age+PMI+RIN+Sexandforcelltypelevelis~Dx:Celltype+Celltype+Age+PMI+RINwhere we extracted the interaction term to determine OUD diagnosis-specific changes in a cell type. For rhesus macaque samples, linear regressions of differential expression and differential AUCell modules were performed across biospecimens (N = 8 biospecimens) controlling for matched pair grouping variable, which accounts for sex, age, and weight. The general model for this linear regression at the individual level is\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{{{{\rm{Value}}}}}} \sim {{{{{\rm{Tx}}}}}}+{{{{{\rm{Pair}}}}}}\; {{{{{\rm{and}}}}}}\; {{{{{\rm{for}}}}}}\; {{{{{\rm{cell}}}}}}\; {{{{{\rm{type}}}}}}\; {{{{{\rm{level}}}}}}\; {{{{{\rm{is}}}}}}\; {{{{{\rm{Value}}}}}} \\ \sim {{{{{\rm{Celltype}}}}}}:{{{{{\rm{Tx}}}}}}+{{{{{\rm{Celltype}}}}}}+{{{{{\rm{Pair}}}}}}.$$\end{document}Value~Tx+PairandforcelltypelevelisValue~Celltype:Tx+Celltype+Pair.
