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 the direct interactions between seed genes (Sup. Fig. 13B), there were 5 protein pairs consisting of: i) PAX6--SOX2; ii) CTIP2--NR2F1; iii) MAPT--NEFM; iv) MAP2--CDH2; and v) SCN2A--SNC3A, which was more than expected by chance alone (p=0.04, 5,000 permutations). In terms of the global network connectivity parameters, the network was composed of a total of 433 interactions from 220 unique proteins. Whereas the mean associated protein direct connectivity was not significant, the observed mean associated protein indirect connectivity (16.7; p=0.0058, 5,000 permutations) was nearly twice that expected. Taken together, these data support the hypothesis that there are shared functional pathways that are differentially regulated in the BD patients CXCR4+ NPCs and neurons compared to their parental controls. Furthermore, the network analysis points to specific physical protein-protein interaction networks that may be key mediators of the underlying phenotypic differences, including the transcription factors PAX6 and SOX2, the chromatin regulator CTIP2 and its direct interactor NR2F1 (Nuclear Receptor subfamily 2, group F, member
