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Chunk #53 — Results — Global transcriptome analysis of BD patient NPCs versus their parental controls

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Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities.
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Using the set of 503 nominally significantly, differentially expressed transcripts as input seeds, we again constructed a protein-protein interaction network using DAPPLE v2.0 (Sup. Fig. 15). Of the input 256 seed genes that could be mapped, 23 proteins showed statistically significant (p<0.05) connectivity after a 5,000 within-degree, node-label permutation (Sup. Table 12). Amongst the direct interactions between seed genes, there were 113, which was more than expected by chance alone as evaluated by permutation testing (p=0.0008). In terms of the global network connectivity parameters, the network was composed of a total of 5,471 interactions between 1,719 unique proteins, with both the observed mean associated protein direct connectivity (1.9; p=0.045) and the observed mean associated protein indirect connectivity (89.5; p=0.0002) significant with 5,000 permutations (Sup. Fig. 15). Taken together with the GO category analysis and similar analysis from using the PsychGene NanoString profiles, these data strongly support the hypothesis that there are shared functional pathways that are differentially regulated in the BD patients CXCR4+ NPCs compared to their parental controls.