Gene-expression profiling of peripheral blood mononuclear cells in sepsis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9960 | GEO | 2009/04/01
SECONDARY ACCESSION(S): PRJNA103971
REPOSITORIES: GEO
Similar Datasets
Project description:To identify signature genes that help distinguish (1) sepsis from non-infectious causes of systemic inflammatory response syndrome, (2) between Gram-positive and Gram-negative sepsis. Experiment Overall Design: A total of 70 critically ill patients (46 sepsis and 24 control) were enrolled in a single-centre observational study. Gene-expression profiling was performed using Affymetrix microarray (U133plus2) with 54,675 transcript. Data was divided into a training set (n=35) and a validation set (n=35). A molecular signature was developed in the training set and was then validated in the validation set.
2009-04-12 | E-GEOD-9960 | biostudies-arrayexpress
Project description:We here sought to better understand the transcriptomic alterations in sorted monocytes (CD14+), CD4+, CD8+ T cells and B cells (CD19+) of sepsis patients (n=6) relative to healthy subjects (n=4).
2020-07-20 | GSE136200 | GEO
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. Keywords: disease state analysis, gram-positive sepsis, gram-negative sepsis
2007-12-01 | GSE6535 | GEO
Project description:Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus classified by the NIAID as a category B priority agent. Septicemia is the most common presentation of the disease with 40% mortality rate even with appropriate treatments. Faster diagnostic procedures are required to improve therapeutic response and survival rates. We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) of whole blood obtained from patients with septicemic melioidosis (n=32), patients with sepsis caused by other pathogens (n=31), and uninfected controls (n=29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% and 78% accuracy in training and independent test sets, respectively. This finding was confirmed by the independent validation set, which showed 80% prediction accuracy. This signature was highly enriched in genes coding for products involved in the MHC Class II antigen processing and presentation pathway. Transcriptional patterns of whole blood RNA distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.
2009-07-01 | GSE13015 | GEO
Project description:Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. While most information on these cells comes from in vitro studies in humans or in vivo studies in mice, little is known about monocytes under human disease conditions. We investigated the role of monocytes during sepsis and its resolution in humans. A transcriptomal and functional analysis of blood monocytes from patients during gram negative sepsis and at recovery was performed. Monocytes from sepsis patients showed upregulation of a large number of pro-inflammatory genes and cytokines/chemokines, consistent with an ongoing systemic inflammation. However, these cells showed impairment to ex vivo endotoxin (LPS) challenge, displaying a quantitative decrease in the number of LPS-inducible genes. Moreover, they downregulated the expression of several pro-inflammatory cytokine/chemokine genes, activation marker genes and transcription factors associated with monocyte/macrophage activation, upon ex vivo LPS stimulation. Functionally, they downregulated expression of inflammatory cytokines/chemokines and antigen presentation-related molecules and functions. In contrast, genes and functions related to phagocytosis, anti-microbial activity and tissue remodeling where remained unaffected or even enhanced . Collectively, our observations suggest a genetic and functional re-programming of these cells during human sepsis progression. Understanding the molecular mechanisms which regulate this re-programming will allow to devise strategies which could modulate the response of these cells and hence, disease progression. Blood monocytes from gram-negative sepsis patients during sepsis (Sepsis) and following their recovery (Recovery/Basal) as well as healthy donor (control) were isolated. Thereafter, these cells were treated ex vivo with or without LPS for 3h and analysed for transcriptomic study.
2014-05-14 | E-GEOD-46955 | biostudies-arrayexpress
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.
2010-05-25 | E-GEOD-6535 | biostudies-arrayexpress
Project description:Immune disorder is a major pathological feature of sepsis, and its complex mechanisms have not been clarified so far. With the help of single-cell transcriptomics technology,we propose to explore the disregulated mechanisms of heterogeneous immune cells in the periphery and bone marrow of peumosepsis hosts.
2024-05-20 | GSE262512 | GEO
Project description:RNA-sequencing of specific peripheral blood mononuclear cells in sepsis
| PRJNA561584 | ENA
Project description:Neonatal gram-negative sepsis is often characterized by a fulminat clinical course compared to adults resulting in higher morbidity and mortality. Genome-wide gene expression analysis can provide insights into the molecular alterations in sepsis. To evaluate in vitro activation of the neonatal and adult immune system, gene expression patterns were compared in mononuclear cells from cord (CBMNC) and adult peripheral blood (APBMNC). To better understand the influence of early molecular signals on the effects of sepsis, Affymetrix gene profiling (8475 genes) was done on RNA isolated from CBMNC and APBMNC without and after incubation with 100 ng/ml lipopolysaccharide (LPS). We demonstrated significant alterations in the expression of 108 CBMNC and APBMNC genes compared with basal levels, 188 significant changes in CBMNC, and 97 in APBMNC, including cytokines, chemokines, and immunoregulatory genes. Furthermore, we found five genes showing a significant interaction effect between cell-type and LPS-stimulation, including tumor necrosis factor receptor superfamily, member 6 (FAS), absent in melanoma 2 (AIM2), malic enzyme 1 (ME1), hemoglobin epsilon 1 (HBE1), and trans-prenyltransferase (TPRT). These results provide further support for a marked difference in the pathogenesis of neonatal and adult sepsis and may stimulate additional studies to investigate some of the altered genes as potential new targets for diagnostic tools and therapeutic strategies. Keywords: LPS response
2005-08-21 | GSE3140 | GEO
Project description:Systemic immune cells dysregulation, especially the inflammatory factors over-production plays the pivotal role in sepsis induced abnormalities. We further analyzed how HDCA affects the systemic immune cells during sepsis by employing scRNA-seq for PBMCs.
2022-02-10 | GSE195965 | GEO