Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches
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ABSTRACT:
PROVIDER: PRJNA679264 | ENA |
REPOSITORIES: ENA
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Project description:In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on 77 peripheral blood samples across 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.
2021-01-14 | GSE161731 | GEO
Project description:In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.
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Project description:This SuperSeries is composed of the following subset Series: GSE18076: G9a selectively represses a class of late-replicating genes at the nuclear periphery (Expression) GSE18079: G9a selectively represses a class of late-replicating genes at the nuclear periphery (WG_CGH) Refer to individual Series
2009-11-02 | E-GEOD-18082 | biostudies-arrayexpress
Project description:How gene positioning to the nuclear periphery regulates transcription remains largely unclear. We have previously observed the differential compartmentalization of transcription factors and histone modifications at the nuclear periphery in mouse C2C12 myoblasts. Here, we have integrated high throughput DNA sequencing into the DNA adenine methyltransferase identification (DamID) assay, and have identified ~15, 000 sequencing-based Lamina-Associated Domains (sLADs) in mouse 3T3 fibroblasts and C2C12 myoblasts. These genomic regions range from a few kb to over 1 Mb and cover ~30% of the genome, and are spatially proximal to the nuclear lamina (NL). Active histone modifications such as H3K4me2, H3K9Ac, H3K36me3 and H3K79me2 are all localized away from the nuclear periphery microscopically, and distributed predominantly out of sLADs genome-wide. Therefore, the spatial compartmentalization of active histone modifications likely characterizes a major portion of chromatin at the nuclear periphery in mammalian cells. Genomic regions around transcription start sites of expressed sLAD genes display reduced associations with the NL and possess active histone modifications; in contrast, gene bodies of expressed sLAD genes possess very low levels of active histone modifications. Our genome-wide analyses of NL-associated chromatin have enabled functional and mechanistic dissections of gene positioning on transcription regulation. generate DamID maps of genome-NL interaction for mouse 3T3 fibroblasts and C2C12 myoblasts
2013-10-30 | E-GEOD-41583 | biostudies-arrayexpress
Project description:SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92-0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
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Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10701 | biostudies-arrayexpress
Project description:Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
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Project description:Tendon is a highly organized, dense connective tissue that has been demonstrated to have very little turnover. In spite of the low turnover, tendon can grow in response to loading, which may take place primarily at the periphery. Tendon injuries and recurrence of injuries are common in both human and animal in sports. It is unclear why some areas of the tendon are more susceptible to such injury and whether this is due to intrinsic regional differences in extracellular matrix (ECM) production or tissue turnover. This study aimed to compare populations of tenocytes derived from the tendon core and periphery. Tenocytes were isolated from equine superficial digital flexor tendons (SDFT), and the proliferation capacity was determined. ECM production was characterized by immuno- and histological staining and by liquid chromatography-mass spectrometry-based proteomics. Core and periphery SDFT cultures exhibited comparable proliferation rates and had very similar proteome profiles, but showed biological variation in collagen type I deposition. In conclusion, the intrinsic properties of tenocytes from different regions of the tendon are very similar and other factors in the tissue may contribute to how specific areas respond to loading or injury.
2020-08-24 | PXD019974 | Pride
Project description:Multiple organ dysfunction syndrome (MODS) can result from a variety of initiating events such as infection or trauma. The clinical condition of some MODS patients may deteriorate and require intense resource and high-risk cardiopulmonary support via extracorporeal membrane oxygenation (ECMO). Until now, no diagnostic criteria/molecular biomarker has been developed to identify MODS patients who require subsequent ECMO support. We used multi-time point (0h, 72h and 8d) whole transcriptomics from total blood of 27 patients (contro-4, MODS-17 and ECMO-6) to derived the molecular signatures to diagnose the MODS patients required ECMO support. We observed that immune response (neutrophil level) was compromised in MODS patients, who required ECMO support. Differential gene expression analysis and gene ontology enrichment has revealed that epigenetic modifications has got activated during the MODS deterioration to ECMO. In addition, signature of 6 genes were identified using logistic regression, which can be used as putative diagnostic markers for patients needed ECMO support.
2020-09-30 | GSE144406 | GEO
Project description:Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and prevented post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.
2017-02-22 | GSE95100 | GEO