Figure 7
Metabolome and proteome convergence pinpoints acquired disease risk in KATP channel deficient hearts. Kir6.2 knockout (n = 10) versus wildtype (n = 10) differential metabolome, differential proteome, and merged multiomics integration were interrogated by Ingenuity Pathway Analysis (IPA). (A) Differential metabolome enriched cellular functions (left, P < 0.05) encompassed metabolism (11 functions), followed in frequency by development (7), homeostasis and survival (6), signaling, transport, and motility (5), morphology and structure (4), and cell cycle, DNA, gene expression functions (3). Differential proteome enriched cellular functions (right, P < 0.05) were highly synonymous, with 37 enriched functions matching 97% (35/36) of enriched metabolome functions (center, Venn diagram). Rearranged relative to metabolome ranking, proteome enrichment likewise exhibited a plurality of metabolism functions (10), along with development (7), homeostasis and survival (6), signaling, transport, and motility (5), cell cycle, DNA, gene expression functions (5), and morphology and structure (4). replic. = replication; recomb. = recombination; transcript. = transcriptional. (B,C) Integrated differential metabolome and proteome data were surveyed in IPA for disease and adverse outcome associations. (B) KATP channel deficiency enriched a collection of diseases and disorders, including metabolic disease, developmental and hereditary disorders, organismal injury, inflammation, and immunological dysfunction, in the context of muscle-related cardiovascular disease. (C) The KATP channel deficient profile predicted susceptibility to cardiac outcomes, with adverse functions ranging across enlargement, dysfunction, arrhythmia, dilation, tachycardia, necrosis/cell death, congenital heart anomaly, and damage.
