Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA110999 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2009-09-10 | GSE12748 | GEO
Project description: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.
2009-09-10 | E-GEOD-12748 | biostudies-arrayexpress
Project description:Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with metabolic and neurologic crises. Liver shows the highest level of glycerol kinase (GK) activity in humans and mice. Absence of genotype-phenotype correlations in patients with GKD indicate the involvement of modifier genes, including other network partners. To understand the molecular pathogenesis of GKD, we performed microarray analysis on liver mRNA from neonatal glycerol kinase (Gyk) knockout (KO) and wild type (WT) mice. Unsupervised learning revealed the overall gene expression profile of the KO mice was different from that of WT. Real time PCR confirmed differences for selected genes. Functional gene enrichment analysis was used to find 56 increased and 37 decreased gene functional categories. Pathway Assist analysis identified changes in gene expression levels of genes involved in organic acid metabolism indicating that GK was part of the same metabolic network which correlates well with the patients with GKD having metabolic acidemia during their episodic crises. Network component analysis (NCA) showed that transcription factors SREBP-1c, ChREBP, HNF-4alpha, and PPAR-alpha, had increased activity in the Gyk KO mice compared with WT mice; while SREBP-2 was less active in the Gyk KO mice. These studies show that Gyk deletion causes alterations in gene expression of genes in several regulatory networks and is the first time NCA has been used to expand on microarray data from a mouse knockout model of a human disease. Keywords: Glycerol kinase (Gyk) knockout mouse; mouse model of human Glycerol Kinase Deficiency; Gyk KO versus WT liver expression analysis; Affymetrix mus 430 2.0 GeneChip
2005-12-22 | GSE3843 | GEO
Project description:The objective was to study gene expression in the prefrontal cortex across the adult age using baboons as a nonhuman primate model. RNA-Seq data was analyzed by Weighted Gene Coexpression Network Analysis (WGCNA), and two modules containing 587 transcripts negatively correlated with age were identified.
2024-08-11 | GSE213926 | GEO
Project description:Targeted disruption of glycerol kinase gene in mice: expression analysis in liver
| PRJNA94063 | ENA
Project description:To excavate the underlying molecular regulation network that during citrus fruit development and ripening, we used RNA-seq to generate high-resolution profiles of global gene expression in four different fruit tissues at six development stages. Using weighted gene coexpression network analysis, we identified modules of coexpressed genes and hub genes of tissue-specific networks. In general, this study was aimed to uncover the new molecular insights into citrus fruit development and ripening, and to reveal the specific nonclimacteric characteristics of citrus fruit.
2019-06-24 | GSE125726 | GEO
Project description:Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with metabolic and neurologic crises. Liver shows the highest level of glycerol kinase (GK) activity in humans and mice. Absence of genotype-phenotype correlations in patients with GKD indicate the involvement of modifier genes, including other network partners. To understand the molecular pathogenesis of GKD, we performed microarray analysis on liver mRNA from neonatal glycerol kinase (Gyk) knockout (KO) and wild type (WT) mice. Unsupervised learning revealed the overall gene expression profile of the KO mice was different from that of WT. Real time PCR confirmed differences for selected genes. Functional gene enrichment analysis was used to find 56 increased and 37 decreased gene functional categories. Pathway Assist analysis identified changes in gene expression levels of genes involved in organic acid metabolism indicating that GK was part of the same metabolic network which correlates well with the patients with GKD having metabolic acidemia during their episodic crises. Network component analysis (NCA) showed that transcription factors SREBP-1c, ChREBP, HNF-4alpha, and PPAR-alpha, had increased activity in the Gyk KO mice compared with WT mice; while SREBP-2 was less active in the Gyk KO mice. These studies show that Gyk deletion causes alterations in gene expression of genes in several regulatory networks and is the first time NCA has been used to expand on microarray data from a mouse knockout model of a human disease. Male WT and KO mouse pups were sacrificed on day of life (dol) 3 and each liver was harvested. Total RNA from 4 KO and 4 WT livers was isolated individually. cDNA was synthesized from the poly(A)+ mRNA in the total RNA, Biotin-tagged and fragmented to an average strand length of 100 bases (range 35-200 bases). Ten µg of each cRNA was hybridized onto an Affymetrix mus 430 2.0 GeneChip to analyze differences in liver gene expression between KO and WT mice. Day of life three was chosen because the mice are phenotypically symptomatic with statistically different parameters for hypoglycemia, acidosis; low bicarbonate and decreased base excess. On day of life 2 they are not significantly different from wild type in all of these important clinical phenotypes.
2007-12-12 | E-GEOD-3843 | biostudies-arrayexpress
Project description:Weighted gene coexpression network analysis-based identification of key modules and hub genes associated with drought sensitivity in rice
| PRJNA667047 | ENA
Project description:The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion are generated. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single-cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here, we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single-cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.
2016-05-26 | GSE77564 | GEO