Functional significance of all modules was evaluated using gene ontology (GO) enrichment analysis using the GO-stats R package (Ashburner et al. 2000; Falcon & Gentleman 2007). Because of the nested structure of the GO terms, a graph decorrelation procedure was used (Alexa et al. 2006). To implement a ranking procedure, we integrated differential network results at the module and gene summarization levels into a comprehensive gene screening procedure. Modules enriched in gene or edge changes were the primary focus of further annotations. At the individual gene level, we focused on module hubs with normalized intramodular connectivity above 0.8. The GOrilla algorithm (Eden et al. 2009) was used to provide a visual representation of GO annotation enrichment and to examine annotation enrichment of selected groups of genes against a background set of all network genes.
