Similar Datasets
Project description:The inflammatory response to surgery is essential for healing and recovery, however hyperinflammation and altered immune competence increases the risk of inflammation mediated complications. We hypothesised that, in some patients, a state of postoperative systemic inflammatory dysregulation (PSID) exists increasing the risk or infection and sepsis, and that this will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. In this study we utilised phenotypic extremes of postoperative plasma C-reactive protein levels to define PSID, which manifested clinically in significantly higher rates of sepsis, complications and longer hospital stays following major abdominal surgery. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression confirms that dysregulation is mediated at multiple levels within specific gene sets and hence, non-specific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.
2021-09-17 | GSE184047 | GEO
Project description:The inflammatory response to surgery is essential for healing and recovery, however hyperinflammation and altered immune competence increases the risk of inflammation mediated complications. We hypothesised that, in some patients, a state of postoperative systemic inflammatory dysregulation (PSID) exists increasing the risk or infection and sepsis, and that this will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. In this study we utilised phenotypic extremes of postoperative plasma C-reactive protein levels to define PSID, which manifested clinically in significantly higher rates of sepsis, complications and longer hospital stays following major abdominal surgery. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression confirms that dysregulation is mediated at multiple levels within specific gene sets and hence, non-specific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.
2021-09-17 | GSE184039 | GEO
Project description:Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation
| PRJNA762898 | ENA
Project description:Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation (METHYLATION)
| PRJNA762909 | ENA
Project description:Integrated methylomic and transcriptomic characterisation of postoperative systemic inflammatory dysregulation (RNA EXPRESSION)
| PRJNA762882 | ENA
Project description:BackgroundPostoperative systemic inflammatory dysregulation (PSID) is characterised by strongly interlinked immune and metabolic abnormalities. However, the hub genes responsible for the interconnections between these two systemic alterations remain to be identified.MethodsWe analysed differentially expressed genes (DEGs) of individual peripheral blood nucleated cells in patients with PSID (n = 21, CRP > 250 mg/L) and control patients (n = 25, CRP < 75 mg/L) following major abdominal surgery, along with their biological functions. Correlation analyses were conducted to explore the interconnections of immune-related DEGs (irDEGs) and metabolism-related DEGs (mrDEGs). Two methods were used to screen hub genes for irDEGs and mrDEGs: we screened for hub genes among DEGs via 12 algorithms using CytoHubba in Cytoscape, and also screened for hub immune-related and metabolic-related genes using weighted gene co-expression network analysis. The hub genes selected were involved in the interaction between changes in immunity and metabolism in PSID. Finally, we validated our results in mice with PSID to confirm the findings.ResultsWe identified 512 upregulated and 254 downregulated DEGs in patients with PSID compared with controls. Gene enrichment analysis revealed that DEGs were significantly associated with immune- and metabolism-related biological processes and pathways. Correlation analyses revealed a close association between irDEGs and mrDEGs. Fourteen unique hub genes were identified via 12 screening algorithms using CytoHubba in Cytoscape and via weighted gene co-expression network analysis. Among these, CD28, CD40LG, MAPK14, and S100A12 were identified as hub genes among both immune- and metabolism-related genes; these genes play a critical role in the interaction between alterations in immunity and metabolism in PSID. The experimental results also showed that the expression of these genes was significantly altered in PSID mice.ConclusionThis study identified hub genes associated with immune and metabolic alterations in patients with PSID and hub genes that link these alterations. These findings provide novel insights into the mechanisms underlying immune and metabolic interactions and new targets for clinical treatment can be proposed on this basis.
| S-EPMC10515200 | biostudies-literature
Project description:Major depressive disorder (MDD) is a mental illness with high incidence and complex etiology, that poses a serious threat to human health and increases the socioeconomic burden. Currently, high-accuracy biomarkers for MDD diagnosis are urgently needed. This paper aims to identify novel blood-based diagnostic biomarkers for MDD. Whole blood DNA methylation data and gene expression data from the Gene Expression Omnibus database are downloaded. Then, differentially expressed/methylated genes (DEGs/DMGs) are identified. In addition, we made a systematic analysis of the DNA methylation on 5'-C-phosphate-G-3' (CpGs) in all of the gene regions, as well as different gene regions, and then we defined a "dominant" region. Subsequently, integrated analysis is employed to identify the robust MDD-related blood biomarkers. Finally, a gene expression classifier and a methylation classifier are constructed using the random forest algorithm and the leave-one-out cross-validation method. Our results demonstrate that DEGs are mainly involved in the inflammatory response-associated pathways, while DMGs are primarily concentrated in the neurodevelopment- and neuroplasticity-associated pathways. Our integrated analysis identified 46 hypo-methylated and up-regulated (hypo-up) genes and 71 hyper-methylated and down-regulated (hyper-down) genes. One gene expression classifier and two DNA methylation classifiers, based on the CpGs in all of the regions or in the dominant regions are constructed. The gene expression classifier possessed the best predictive ability, followed by the DNA methylation classifiers, based on the CpGs in both the dominant regions and all of the regions. In summary, the integrated analysis of DNA methylation and gene expression has identified 46 hypo-up genes and 71 hyper-down genes, which could be used as diagnostic biomarkers for MDD.
| S-EPMC7912210 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-03 | GSE233769 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-04-25 | GSE129876 | GEO
Project description:Plant height affects crop production and breeding practices, while genetic control of dwarfism draws a broad interest of researchers. Dwarfism in soybean (Glycine max) is mainly unexplored. Here, we characterized a dwarf mutant dm screened from ethyl methanesulfonate (EMS) mutated seeds of the soybean cultivar Zhongpin 661(ZP). Phenotypically, dm showed shorter and thinner stems, smaller leaves, and more nodes than ZP under greenhouse conditions. Genetically, whole-genome sequencing and comparison revealed that 210K variants of SNPs and InDel in ZP relative to the soybean reference genome Williams82, and EMS mutagenesis affected 636 genes with variants predicted to have a large impact on protein function in dm. Whole-genome methylation sequencing found 704 differentially methylated regions in dm. Further whole-genome RNA-Seq based transcriptomic comparison between ZP and dm leaves revealed 687 differentially expressed genes (DEGs), including 263 up-regulated and 424 down-regulated genes. Integrated omics analyses revealed 11 genes with both differential expressions and DNA variants, one gene with differential expression and differential methylation, and three genes with differential methylation and sequence variation, worthy of future investigation. Genes in cellulose, fatty acids, and energy-associated processes could be the key candidate genes for the dwarf phenotype. This study provides genetic clues for further understanding of the genetic control of dwarfism in soybean. The genetic resources could help to inbreed new cultivars with a desirable dwarf characteristic.
| S-EPMC9721362 | biostudies-literature