Fig. 4

qRT-PCR Validation and gene set enrichment analysis. a Twenty-five differentially expressed genes were chosen for validation using qRT-PCR. Expression values from each WBS iPSC neuronal line (n = 3) were normalized to HMBS and TBP, and are presented as average fold change relative to WT control. All 25 genes showed altered expression in the same direction as identified on the array; the corresponding heatmap shows the log2 fold change in expression values from the array, with red indicating lower and blue indicating higher expression in WBS samples. Data are shown as mean ± SEM. b Log2 fold change of the top 15 downregulated genes in the voltage-gated potassium channel complex (GO:0008076) from the microarray. c Enrichment Plots of the two most highly enriched gene sets in the dataset. The top 10 genes in each gene set, ranked by absolute fold change, are shown in the corresponding tables (Additional file 6: Table S2, Additional file 7: Table S3, Additional file 8: Table S4 and Additional file 9: Table S5). d Enriched synaptic gene sets are highly interconnected. Enrichment Map [25] in Cytoscape was used to visualize overlap between enriched gene sets (FDR <0.1) as a network of interconnected nodes. The size of each node corresponds to the size of the gene set. The node color corresponds to the normalized enrichment score, with a darker green corresponding to stronger negative enrichment (lower expression in WBS relative to WT). The size of the edges between nodes corresponds to the number of genes the gene sets share in common. The largest interconnected network of nodes, which was comprised of gene sets governing synaptic function, is shown (46 out of a total 136 nodes). The full enrichment map is shown in Additional file 4: Figure S4