Genome wide analysis of transcriptome and microRNAs in early stage of Alzheimer’s disease (mRNA)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52022 | GEO | 2013/12/01
SECONDARY ACCESSION(S): PRJNA226224
REPOSITORIES: GEO
Similar Datasets
Project description:We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD. These results demonstrate that candidate genes on the simultaneous profiling of mRNA and miRNA expressions in genome wide can be used for the understanding of non-coding RNA related gene expression in early stage AD. We suggested that our results could be future candidate to be developed as early biomarkers in progressive AD pathology. This result can be used for the further application in neurodegenerative diseases.
2013-12-01 | GSE52023 | GEO
Project description:We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD. These results demonstrate that candidate genes on the simultaneous profiling of mRNA and miRNA expressions in genome wide can be used for the understanding of non-coding RNA related gene expression in early stage AD. We suggested that our results could be future candidate to be developed as early biomarkers in progressive AD pathology. This result can be used for the further application in neurodegenerative diseases. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification.
2013-12-01 | E-GEOD-52023 | biostudies-arrayexpress
Project description:We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD. These results demonstrate that candidate genes on the simultaneous profiling of mRNA and miRNA expressions in genome wide can be used for the understanding of non-coding RNA related gene expression in early stage AD. We suggested that our results could be future candidate to be developed as early biomarkers in progressive AD pathology. This result can be used for the further application in neurodegenerative diseases. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification.
2013-12-01 | E-GEOD-52022 | biostudies-arrayexpress
Project description:Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p≤ 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p≤ 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs’ biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p≤ 0.0001). At FDR≤ 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
2015-05-22 | GSE62699 | GEO
Project description:Alcohol consumption is known to lead to gene expression changes in the brain. After performing gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA expressions in the Nucleus Accumbens (NAc) from subjects with alcohol dependence (AD) and matched controls six mRNA and three miRNA modules significantly correlated with AD after Bonferroni correction (adj. p? 0.05) were identified. Cell-type-specific transcriptome analysis revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four were enriched for astrocyte and microglial specific marker genes and were upregulated in AD. Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were enriched mostly for genes involved in processes related to immune functions, i.e. reactome cytokine signaling in immune system (all adj. p? 0.05). In the mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected miRNAs’ biological functions, the correlation analyses between mRNA and miRNA hub genes revealed a significantly higher number of positive than negative correlations (chi-square p? 0.0001). At FDR? 0.1, integration of the mRNA and miRNA hubs genes expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs for the mRNA and miRNA hubs, respectively. Adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in the Collaborative Study on Genetics of Alcohol (COGA) sample (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified coordinated mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. Tissue samples were received from the Australian Brain Donor Programs New South Wales Tissue Resource Centre, which is supported by The University of Sydney, National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism, and the New South Wales Department of Health. Cases were excluded if they had an infectious disease (i.e. HIV/AIDS, hepatitis B or C, or Creutzfeldt-Jakob disease), an unsatisfactory agonal status determined from the circumstances surrounding the death, post-mortem delays >48 hours, or significant head injury. In addition to case status, age, sex, ethnicity, brain weight, brain pH, post-mortem interval (PMI), tissue hemisphere, clinical cause of death, blood toxicology at time of death, smoking status, neuropathology and liver pathology were also provided for each subject. MiRNA and mRNA expression in 18 matched case-control pairs (N=36) with sample RINs ?6 were assessed on the Affymetrix GeneChip® Human Genome U133A 2.0 (HG-U133A 2.0) and Affymetrix GeneChip miRNA 3.0 microarray.
2015-05-22 | E-GEOD-62699 | biostudies-arrayexpress
Project description:Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n=35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc=6; PFC=3) and miRNA (NAc=3; PFC=2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc=6; PFC=4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA=37, miRNA=9; PFC: mRNA=17, miRNA=16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
2020-11-24 | GSE161997 | GEO
Project description:Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n=35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc=6; PFC=3) and miRNA (NAc=3; PFC=2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc=6; PFC=4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA=37, miRNA=9; PFC: mRNA=17, miRNA=16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
2020-11-24 | GSE161986 | GEO
Project description:We performed a systems-level study of disease-associated proteome changes in human frontal cortex of Alzheimer’s disease (AD) patients using an integrated approach that combines mass spectrometry-based quantitative proteomics, differential expression analysis, and co-expression network analysis. Our analyses of 16 human brain tissues from AD patients and age-matched controls showed organization of the cortical proteome into a network of 24 biologically meaningful modules of co-expressed proteins. Of these, 5 modules are positively correlated to AD phenotypes with hub proteins that are up-regulated in AD, and 6 modules are negatively correlated to AD phenotypes with hub proteins that are down-regulated in AD.
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2020-08-05 | PXD006350 | Pride