To gain a systems-level understanding of the transcriptome, we used WGCNA to build gene co-expression networks for each tissue region. It is thought that genes that co-express and co-vary perform similar biological functions or act in the same biological pathway (“guilty by association” principle) 29. WGCNA is a complementary approach to differential expression and provides a reference for interpretation and validation of differential expression analysis. We identified the gene–gene regulatory relationships that were activated by PPAR agonists, which we refer to as treatment-responsive modules. This approach has been validated by several independent research groups as a method for predicting genes that underlie a biological or molecular process 19, 36, 37, 53, 64, 67.
