Co-methylation Networks Associated with Cognition and Structural Brain Development During Adolescence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1199520 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Typical adolescent neurodevelopment is marked by decreases in grey matter (GM) volume, increases in myelination, measured by fractional anisotropy (FA), and improvement in cognitive performance. To understand how epigenetic changes, methylation (DNAm) in particular, may be involved during this phase of development, we studied cognitive assessments, DNAm from saliva, and neuroimaging data from a longitudinal cohort of normally developing adolescents, aged nine to fourteen. We extracted networks of methylation with patterns of correlated change using a weighted gene correlation network analysis (WCGNA). Modules from these analyses, consisting of co-methylation networks, were then used in multivariate analyses with GM, FA, and cognitive measures to assess the nature of their relationships with cognitive improvement and brain development in adolescence. This longitudinal exploration of co-methylated networks revealed an increase in correlated epigenetic changes as subjects progressed into adolescence. Co-methylation networks enriched for pathways involved in neuronal systems, potassium channels, neurexins and neuroligins were both conserved across time as well as associated with maturation patterns in GM, FA, and cognition, revealing epigenetic mechanisms that could be involved in adolescent neural development.
2024-12-20 | GSE284550 | GEO
Project description:Erythropoietin re-wires cognition-associated transcriptional networks
| PRJNA910128 | ENA
Project description:Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ꞌtoolꞌ, we discover populations of newly differentiating pyramidal neurons, overpopulating to ~200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.
2023-06-16 | GSE220522 | GEO
Project description:A novel systems approach was applied to transcriptome profiling that included the traditional analysis of differentially expressed genes, gene co-expression networks, cell type - specific transcriptomes and a wide range of gene annotations. By integrating our data with previous findings, we generated the first systems hypothesis of human alcoholism that integrates epigenetic regulation of gene expression with structural and functional alterations in alcoholic brain. Total RNA was extracted from human post-mortem brain and gene expression profiles were compared between alcoholics and matched controls.
2011-07-12 | E-GEOD-29555 | biostudies-arrayexpress
Project description:Background: Adolescent cannabis use leads to long-lasting behavioral changes involving cognitive and reward processes. However, the underlying molecular mechanisms are not well understood. To address this limitation, we performed gene network analyses using transcriptomic data from mice exposed during adolescence to Δ-9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis. Methods: We injected vehicle or THC in female and male mice during the entire adolescence period. Two weeks following the last exposure, we measured recognition memory, social interaction and anxiety-related behaviors. We generated 120 RNA-seq datasets from 5 brain regions for each mouse. We performed differential gene expression analysis and constructed co-expression networks to identify THC-induced transcriptional alterations at the level of individual genes, gene networks, biological pathways, and cellular specificity. Further, we integrated THC-correlated gene networks with human traits from genome-wide association studies and performed key driver analysis to identify potential regulators of disorder-associated networks. Results: THC impaired cognitive behaviors of mice, with memory being more impacted in females, which coincided with larger transcriptional alterations in the female brain. Gene network analyses identified brain region-, cell type- and sex- specific co-expressed genes (“modules”) dysregulated by THC. THC-induced memory deficits in females were correlated with disruption of gene networks involved in endocannabinoid signaling and inflammation. Additional THC-correlated modules in both sexes involved converging pathways related to dopamine signaling and addiction processes. Moreover, the connectivity map of THC-correlated modules uncovered intra- and inter-region molecular circuitries influenced by THC. Further, modules altered by THC treatment were enriched in genes relevant for human cognition and schizophrenia. Conclusions: These findings provide novel insights concerning the genes, cell types, and pathways underlying persistent behavioral deficits induced by adolescent exposure to THC in a sex-specific manner, and highlight the connection between adolescent cannabis use and neuropsychiatric disorders in humans.
2021-12-06 | GSE189821 | GEO
Project description:A novel systems approach was applied to transcriptome profiling that included the traditional analysis of differentially expressed genes, gene co-expression networks, cell type - specific transcriptomes and a wide range of gene annotations. By integrating our data with previous findings, we generated the first systems hypothesis of human alcoholism that integrates epigenetic regulation of gene expression with structural and functional alterations in alcoholic brain.
2011-07-12 | GSE29555 | GEO
Project description:The hypothesis of this study is that patients who suffered from acne vulgaris during adolescence are at greater risk of developing acneiform skin rash due to cetuximab.
| 2108857 | ecrin-mdr-crc
Project description:This study sought to investigate temporal changes in hippocampal gene co-expression networks during the development of rats submitted to hyperthermic seizures
2017-12-20 | GSE84289 | GEO
Project description:Gene co-expression networks (GCNs) have not been extensively studied in non-model plants. However, the rapid accumulation of transcriptome datasets in these species represents an opportunity to explore underutilized network aggregation approaches that highlight robust co-expression interactions and improve functional connectivity. We applied and evaluated two different aggregation methods on public grapevine RNA-Seq datasets belonging to three different tissue conditions (leaf, berry and ‘all organs’). Our results show that co-occurrence-based aggregation generally yielded the best-performing networks. We applied GCNs to study several TF gene families, showing its capacity of detecting both already-described and novel regulatory relationships between R2R3-MYBs, bHLH/MYC and multiple secondary metabolism pathway reactions. Specifically, using TF gene- and pathway-centered network analyses, we ascertained the previously demonstrated role of VviMYBPA1 in controlling the accumulation of proanthocyanidins while providing novel insights into its role as a potential regulator of p-coumaroyl-CoA biosynthesis as well as the shikimate and aromatic amino-acid pathways. This network was validated using DNA Affinity Purification Sequencing data, demonstrating that co-expression networks of activational transcription factors can serve as a proxy of gene regulatory networks. This study presents an open repository to reproduce networks and a GCN application within the Vitviz platform, a user-friendly tool for exploring co-expression relationships.
2023-04-28 | GSE230186 | GEO
Project description:siRNA BDNF and siRNA HDAC4 treatment impaired cognition
2017-06-10 | GSE83217 | GEO