Figure 6
Cross platform validation of NAD+-dependent KATP channel deficiency. (A) Enriched pathways arising from the Kir6.2 knockout (KO) versus wildtype (WT) differential metabolome (n = 10 per cohort) were identified in Ingenuity Pathway Analysis canonical pathways (P < 0.05) documenting a predominant link to NAD+ amongst all 27 differential metabolites associated with overrepresented pathways, with NAD+ linking to 22 of 36 pathways and other differentially expressed metabolites linking to 12 or fewer. (B) Validating cross-algorithm evidence of NAD+ dependence, Metabolite Set Enrichment Analysis specified NAD+ linkage to 60 of 63 enriched metabolic pathways (P < 0.05), whereas 26 other differential metabolites linked to 9 or fewer pathways each. (C) Within the corresponding proteome (n = 10 per cohort), 9 differentially expressed proteins were NAD+ associated. Listed by gene symbol, biological processes, and protein name (mito. = mitochondrial), NAD+ associated proteins were rank ordered by relative abundance in KO versus WT, with 8 linked to ‘Metabolism, Catabolism’ processes.
