Genomics visium platform

As previously described by Huuki-Myers et al. 2023 (46 ), paired (meaning both types of -omics were measured on the same N=19 tissue blocks) snRNA-seq measured on the 10x Genomics Chromium platform and spatially-resolved transcriptomics data measured on the 10x Genomics Visium platform were generated from tissue blocks collected from 3 different positions across the anterior-posterior axis of the DLPFC (designated posterior, anterior, and middle) from 10 adult neurotypical control donors (Table S1). In our analyses here, we only use the snRNA-seq libraries to generate the pseudobulk RNA-seq profiles. In addition to the snRNA-seq libraries generated from these tissue blocks, there was also paired bulk RNA-sequencing, and single molecule fluorescent in situ hybridization (smFISH)/immunofluorescence (IF) using RNAScope/IF technology generated and described in Huuki-Myers et al. 2024 (26 ) measured in the same tissue blocks. The smFISH/IF data was used to measure the cell type composition in the same tissue samples serving as a “gold standard” to compare the estimated cell composition in the bulk RNA-seq predicted by the deconvolution algorithms in (26 ). The fact that all three (snRNA-seq, bulk RNA-seq, and smFISH/IF) technologies were measured on the same tissue blocks helps to minimize potential donor-specific unwanted variation or batch effects.