Dataset: Weighted Gene Coexpression Network Analysis Identifies Biomarkers in Glycerol Kinase Deficient Mice

Symptomatic glycerol kinase deficiency (GKD) is associated with episodic metabolic and central nervous system deterioration. We report here the first application of Weighted Gene Co-Expression Network Analysis (WGCNA) to investigate a knockout (KO) murine model of a human genetic disease. WGCNA identified networks and key hub transcripts from liver mRNA of glycerol kinase (Gyk) KO and wild type (WT) mice. Day of life 1 (dol1) samples from KO mice contained a network module enriched for organic acid metabolism before Gyk KO mice develop organic acidemia and die on dol3-4 and the module containing Gyk was enriched with apoptotic genes. Roles for the highly connected Acot, Psat and Plk3 transcripts were confirmed in cell cultures and subsequently validated by causality testing. We provide evidence that GK may have an apoptotic moonlighting role that is lost in GKD. This systems biology strategy has improved our understanding of GKD pathogenesis and suggests possible treatments. Male WT and KO mouse pups were sacrificed on day of life (dol) 1 and each liver was harvested. Total RNA from 4 KO and 3 WT livers was isolated individually. Affymetrix mus 430 2.0 GeneChips were used to analyze differences in liver gene expression between KO and WT mice. Dol1 and 3 Gyk KO mice represent different disease states. Dol 1 was chosen because mice are phenotypically asymptomatic with respect to Glycerol Kinase Deficiency (GKD) and allowed us to look at alterations that occur before the overt disease state. Dol 3 mice are phenotypically symptomatic with respect to GKD.

Species:

mouse

Samples:

7

Source:

E-GEOD-12748

PubMed:

19546021

Updated:

Dec.12, 2014

Registered:

Nov.10, 2014