Next, gene categories enrichment analysis (GCEA) was performed to identify molecular architectures related to the transcriptional correlations with PC1 [40]. GCEA is a score-based approach that includes all correlations regardless of the level of significance so that modest but coordinated correlations in a prior set of related genes (e.g., a gene ontology category) may be detected. GCEA computed a category score for a prior gene set by averaging z-transformed correlation coefficients within the set. The category score of the original correlations was compared against that of a null distribution to determine statistical significance. It has been shown that the spatial autocorrelation and co-expression of genes can inflate the false-positive rate in the GCEA if not controlled for properly in the null model [40]. To address this, the 66 loadings of Combined-PC1 were shuffled while preserving their spatial contiguity and then correlated with transcriptional profiles of all genes for each iteration of the null model. Then a null category score for the prior gene set was obtained. This procedure was repeated 10,000 times yielding a null distribution of category scores. The
