Transcriptomic Profiles of Sepsis in the Human Brain
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ABSTRACT:
PROVIDER: PRJNA560245 | ENA |
REPOSITORIES: ENA
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Project description:The purpose of this study is to examine the transcriptomic profiles (RNAseq) of post-mortem brain tissue samples from patients who have died of sepsis compared to non-sepsis controls using two analytic approaches. Tissue samples originated from the Adult Changes in Thought study (ACT) brain bank. In order to determine cause of death, hospital charts for 89 ACT subjects who died while hospitalized were reviewed using a structured instrument for diagnosis of sepsis. RNA was extracted from 24 post-mortem parietal cortex tissue samples. RNA sequencing was performed on the 24 samples using Illumina's Hi-Seq platform. Raw data was exported, pre-processed, and analyzed by two methods, differential expression and weighted gene co-expression network analysis (WGCNA). 176 genes were differentially expressed with fold change of > 1.5 and adjusted p < 0.5. The top differentially expressed genes were immune-related. WGCNA reveled 6 modules were significantly correlated with sepsis. Significant nodules were enriched in terms associated with innate immunity, cytokines, DAMPs, synaptic function, ion channel function, neuronal growth, and T-cell signalling among others. These data suggest sepsis is associated with specific transcriptional responses in the human brain. These results provide support for previously identified targets as well as provide evidence to suggest investigation into new targets for mechanistic exploration of sepsis-associated brain injury.
2019-11-26 | GSE135838 | GEO
Project description: Not available
| S-EPMC7124721 | biostudies-literature
Project description:Genomic and transcriptomic profiles of human brain microvascular pericytes upon neural transdifferentiation
| PRJNA777267 | ENA
Project description:This study aimed to compare gene expression profiles between patients with sepsis and healthy volunteers, to determine the accuracy of these profiles in diagnosing sepsis, and to predict sepsis outcomes by combining bioinformatics data with molecular experiments and clinical information.
2023-05-19 | GSE232753 | GEO
Project description:Rationale: Sepsis is a leading cause of morbidity and mortality; early diagnosis and prediction of progression is difficult to determine. The integration of metabolomic and transcriptomic data in an experimental model of sepsis may be a novel method to identify molecular signatures of clinical sepsis. Objectives: Develop a biomarker panel for earlier diagnosis and prognostic characterization of sepsis patients to inform personalized clinical management and improve understanding of the pathophysiology of sepsis progression. Methods: Mild to severe sepsis, lung injury and death was recapitulated in Macaca fascicularis by intravenous inoculation of Escherichia coli. Plasma samples were obtained at time of challenge and at one, three, and five days later or time of euthanasia. Necropsy was performed and blood, lung, kidney and spleen samples were obtained. An integrative analysis of comprehensive metabolomic and transcriptomic datasets was performed to identify and parameterize a biomarker panel. Measurements and Main Results: Pathogen invasion, respiratory distress, lethargy and mortality was dose dependent. Severe infection and death were associated with metabolomic and transcriptomic changes indicative of mitochondrial, peroxisomal and liver dysfunction. Analysis of reciprocal pulmonary transcriptome and plasma metabolome data revealed an integrated host response that suggested dysregulated fatty acid catabolism resulting from peroxisome-proliferator activated receptor signaling. A representative 4-metabolite model effectively diagnosed sepsis in primates (AUC 0.966) and in two human sepsis cohorts (AUC=0.78 and 0.82). Conclusion: A model to guide early management of patients with sepsis was developed by analysis of reciprocal metabolomic and transcriptomic data in primates that diagnosed sepsis in humans. Transcriptomic analysis of lungs from Cynomolgus macaques challenged with E. coli
2015-07-03 | E-GEOD-59075 | biostudies-arrayexpress
Project description:We assayed leukocyte global gene expression for a prospective discovery cohort of 106 adult patients admitted to UK intensive care units with sepsis due to community acquired pneumonia or faecal peritonitis. We assigned all samples to sepsis response signature groups after performing unsupervised analysis of the transcriptomic data.
2017-05-01 | E-MTAB-5274 | biostudies-arrayexpress
Project description:<p>Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We produced single cell transcriptomic profiles for 40,000 cells at mid-gestation to define deep expression profiles corresponding to all known major cell types at this developmental period and compare this with bulk tissue profiles. We identified multiple transcription factors (TFs) and co-factors expressed in specific cell types, including multiple new cell-type-specific relationships, providing an unprecedented resource for understanding human neocortical development and evolution. This includes the first single-cell characterization of human subplate neurons and subtypes of developing glutamatergic and GABAergic neurons. We also used these data to deconvolute single cell regulatory networks that connect regulatory elements and transcriptional drivers to single cell gene expression programs in the developing CNS. We characterized major developmental trajectories that tie cell cycle progression with early cell fate decisions during early neurogenesis. Remarkably, we found that differentiation occurs on a transcriptomic continuum, so that differentiating cells not only express the few key TFs that drive cell fates, but express broad, mixed cell-type transcriptomes prior to telophase. Finally, we mapped neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types in ASD, ID, and epilepsy, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.</p>
| phs001836 | dbGaP
Project description:Transcriptional effects in circulating leukocytes from mice challenged to peritoneal contamination and infection (PCI) compared to sham (vehicle control). We gratefully acknowledge the BMBF grant for the Center for Sepsis Control and Care (CSCC) for this study
2017-09-01 | GSE36608 | GEO
Project description:Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences.
2016-05-29 | E-MTAB-4785 | biostudies-arrayexpress
Project description:We assayed leukocyte global gene expression for a prospective validation cohort of 221 adult patients admitted to UK intensive care units with sepsis due to community acquired pneumonia or faecal peritonitis. 10 samples from patients scheduled for elective cardiac surgery were also assayed as non-septic controls. We assigned all samples to sepsis response signature groups after performing unsupervised analysis of the transcriptomic data.
2017-05-01 | E-MTAB-5273 | biostudies-arrayexpress