As an alternative approach to determining if there was evidence for common underlying molecular pathways, we turned to the consideration of the protein-protein interaction network amongst the proteins encodes by the differentially expressed genes. Using Disease Association Protein-Protein Link Evaluator (DAPPLE) v2.0, the set of the 53 differentially regulated genes were used as seed nodes and we built a direct and indirect (through other proteins) interaction network amongst the proteins encoded by the seed genes with edges between the nodes derived from protein-protein interaction data in the InWeb database of protein interaction that combines multiple data sources (MINT, BIND, IntAct, KEGG, ECrel, Reactome) as described by Lage et al.57 (Sup. Fig. 13A). The statistical significance of the connectivity of individual proteins to other seed proteins, as well as a set of network connectivity parameters, was then assessed with within-degree, node-label permutation methods. Of the input 43 seed genes that could be mapped, 9 proteins (MAP2, GPM6A, CACNA1G, CACNA1E, KLF4, CDH2, DACH1, SCN3A, SOX2) showed statistically significant (p<0.05) connectivity after a 5,000 within-degree, node-label permutation (Sup. Tables 8 & 9). Amongst
