We then asked whether, at a system level, the DEGs underline coherent alterations in groups of co-expressed genes. Using weighted gene co-expression network analysis, WGCNA (Langfelder and Horvath, 2008), we identified 24 modules of co-expressed genes across probands and controls at TD11 and TD31, all of which survived permutation analysis (Table S3). We estimated the modules’ eigengenes (i.e. the first principal component of the module’s genes expression profiles) and assessed their changes over time and across diagnosis (see Figure 2A). The yellow and green modules (annotated by “vascular development” and “lipid metabolism” gene ontology (GO) categories, respectively) were enriched in downregulated DEGs (Table S4), and their eigengenes were consistently downregulated across time points (Figure 2A). The blue and magenta modules (annotated by “neuronal differentiation” and “regulation of transcription” GO terms, respectively) were enriched in upregulated genes at both TD11 and TD31 (Table S4), and their eigengenes were consistently upregulated across time points, in keeping with their developmental annotation. The brown and tan modules (annotated by “synaptic transmission” and “gated channel activity” GO terms, respectively), however, were enriched in upregulated genes
