Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

ABSTRACT: We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. Transcriptome analysis highlighted a pronounced intratumor architecture reflecting the surgical sampling plan of the study and identified gene modules associated with hallmarks of cancer.

ORGANISM(S): Homo sapiens

SUBMITTER: Amandine Etcheverry

PROVIDER: E-MTAB-5092 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

From the core to beyond the margin: a genomic picture of glioblastoma intratumor heterogeneity.

Aubry Marc M de Tayrac Marie M Etcheverry Amandine A Clavreul Anne A Saikali Stéphan S Menei Philippe P Mosser Jean J

Oncotarget 20150501 14

Glioblastoma (GB) is a highly invasive primary brain tumor that almost systematically recurs despite aggressive therapies. One of the most challenging problems in therapy of GB is its extremely complex and heterogeneous molecular biology. To explore this heterogeneity, we performed a genome-wide integrative screening of three molecular levels: genome, transcriptome, and methylome. We analyzed tumor biopsies obtained by neuro-navigation in four distinct areas for 10 GB patients (necrotic zone, tu ...[more]

PMID: 25940437

Similar Datasets

aCGH profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

Project description:We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. At the genome level, we identified common GB copy number alterations and but a strong inter-individual molecular heterogeneity.

2016-09-19 | E-MTAB-5098 | biostudies-arrayexpress

Methylome profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

Project description:We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. We provide a signature of key cancer-heterogeneity genes highly associated with the intratumor spatial gradient and show that it is enriched in genes with correlation between methylation and expression levels.

2016-09-19 | E-MTAB-5109 | biostudies-arrayexpress

Identifying the necrotic zone boundary in tumour spheroids with pair-correlation functions.

Project description:Automatic identification of the necrotic zone boundary is important in the assessment of treatments on in vitro tumour spheroids. This has been difficult especially when the difference in cell density between the necrotic and viable zones of a tumour spheroid is small. To help overcome this problem, we developed novel one-dimensional pair-correlation functions (PCFs) to provide quantitative estimates of the radial distance of the necrotic zone boundary from the centre of a tumour spheroid. We validate our approach on synthetic tumour spheroids in which the position of the necrotic zone boundary is known a priori It is then applied to nine real tumour spheroids imaged with light sheet-based fluorescence microscopy. PCF estimates of the necrotic zone boundary are compared with those of a human expert and an existing standard computational method.

| S-EPMC5095222 | biostudies-literature

Choroid plexus tertiary lymphoid structures in lupus: a novel neuro-immune interface

Project description:The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood, confounding physician treatment options and leaving patients with little options beyond empirical remedies. We utilized a well-established model of both the systemic and neuropsychiatric manifestations of SLE in an attempt to further understand which immune effectors may be responsible for central nervous system (CNS) disease. We found that a mixed cellular infiltrate in the choroid plexus of these mice represented a tertiary lymphoid structure with in-situ somatic hypermutation and class switch recombination. We further found that this process was driven by cytokine signaling sourced within the CNS that could be abrogated by treatment with biological therapeutics. Therefore, inconsistencies in previous work to determine which neuropathic autoantibodies are involved in the progression of neuropsychiatric lupus may have been lacking, as the source of these autoantibodies are intra-cranial, with limited systemic distribution.

2019-06-17 | GSE99030 | GEO

Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease.

Project description:TLR7 recognizes pathogen-derived single-stranded RNA (ssRNA), a function integral to the innate immune response to viral infection. Notably, TLR7 can also recognize self-derived ssRNA, with gain-of-function mutations in human TLR7 recently identified to cause both early-onset systemic lupus erythematosus (SLE) and neuromyelitis optica. Here, we describe two novel mutations in TLR7, F507S and L528I. While the L528I substitution arose de novo, the F507S mutation was present in three individuals from the same family, including a severely affected male, notably given that the TLR7 gene is situated on the X chromosome and that all other cases so far described have been female. The observation of mutations at residues 507 and 528 of TLR7 indicates the importance of the TLR7 dimerization interface in maintaining immune homeostasis, where we predict that altered homo-dimerization enhances TLR7 signaling. Finally, while mutations in TLR7 can result in SLE-like disease, our data suggest a broader phenotypic spectrum associated with TLR7 gain-of-function, including significant neurological involvement.

| S-EPMC10850255 | biostudies-literature

Neutrophil Extracellular Traps Form a Barrier between Necrotic and Viable Areas in Acute Abdominal Inflammation.

Project description:Neutrophils form neutrophil extracellular traps (NETs) of decondensed DNA and histones that trap and immobilize particulate matter and microbial pathogens like bacteria. NET aggregates reportedly surround and isolate large objects like monosodium urate crystals, which cannot be sufficiently cleared from tissues. In the setting of acute necrotizing pancreatitis, massive tissue necrosis occurs, which is organized as pancreatic pseudocysts (1). In contrast to regular cysts, these pseudocysts are not surrounded by epithelial layers. We hypothesize that, instead, the necrotic areas observed in necrotizing pancreatitis are isolated from the surrounding healthy tissues by aggregated NETs. These may form an alternative, putatively transient barrier, separating necrotic areas from viable tissue. To test this hypothesis, we investigated histological samples from the necropsy material of internal organs of two patients with necrotizing pancreatitis and peritonitis accompanied by multiple organ failure. Tissues including the inflammatory zone were stained with hematoxylin and eosin and evaluated for signs of inflammation. Infiltrating neutrophils and NETs were detected by immunohistochemistry for DNA, neutrophil elastase (NE), and citrullinated histone H3. Interestingly, in severely affected areas of pancreatic necrosis or peritonitis, chromatin stained positive for NE and citrullinated histone H3, and may, therefore, be considered NET-derived. These NET structures formed a layer, which separated the necrotic core from the areas of viable tissue remains. A condensed layer of aggregated NETs, thus, spatially shields and isolates the site of necrosis, thereby limiting the spread of necrosis-associated proinflammatory mediators. We propose that necrotic debris may initiate and/or facilitate the formation of the NET-based surrogate barrier.

| S-EPMC5056318 | biostudies-literature

Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis.

Project description:ObjectiveIn acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease and late death. Understanding how immunological host defence mechanisms fail to protect the intestinal barrier is of great importance in reducing the mortality risk of the disease. Here, we studied the role of the Treg/Th17 balance for maintaining the intestinal barrier function in a mouse model of severe AP.DesignAP was induced by partial duct ligation in C57Bl/6 or DEREG mice, in which regulatory T-cells (Treg) were depleted by intraperitoneal injection of diphtheria toxin. By flow cytometry, functional suppression assays and transcriptional profiling we analysed Treg activation and characterised T-cells of the lamina propria as well as intraepithelial lymphocytes (IELs) regarding their activation and differentiation. Microbiota composition was examined in intestinal samples as well as in murine and human pancreatic necrosis by 16S rRNA gene sequencing.ResultsThe prophylactic Treg-depletion enhanced the proinflammatory response in an experimental mouse model of AP but stabilised the intestinal immunological barrier function of Th17 cells and CD8+/γδTCR+ IELs. Treg depleted animals developed less bacterial translocation to the pancreas. Duodenal overgrowth of the facultative pathogenic taxa Escherichia/Shigella which associates with severe disease and infected necrosis was diminished in Treg depleted animals.ConclusionTregs play a crucial role in the counterbalance against systemic inflammatory response syndrome. In AP, Treg-activation disturbs the duodenal barrier function and permits translocation of commensal bacteria into pancreatic necrosis. Targeting Tregs in AP may help to ameliorate the disease course.

| S-EPMC10314084 | biostudies-literature

Single Nuclei Sequencing of old and young mice hearts under senolytica (Ageing impairs the neuro-vascular interface in the heart)

Project description:Aging is a major risk factor for impaired cardiovascular health. The aging myocardium is characterized by microcirculatory and diastolic dysfunction and increased susceptibility to arrhythmias. Nerves align with vessels during development. However, the impact of aging on the cardiac neuro-vascular interface is entirely unknown. Here, we report that aging reduces nerve density specifically in the left ventricle and dysregulates vascular-derived neuro-regulatory genes. Aging leads to a down-regulation of miR-145 and de-repression of the neuro-repulsive factor Semaphorin-3A. miR-145 deletion, which increased Sema3a expression, or endothelial Sema3a overexpression reduced axon density, thus mimicking the observed aged heart phenotype. Removal of senescent cells, which accumulated with chronological age in parallel to the decline in nerve density, rescued age-induced denervation, reduced Sema3a expression, preserved heart rate variability and reduced electrical instability. These data suggest that senescence-associated regulation of neuro-regulatory genes is associated with reduced nerve density and, thereby, contributes to age-associated cardiac dysfunction.

2023-07-05 | E-MTAB-13093 | biostudies-arrayexpress

Transcription profiling of human cervical cancer patient biopsies to explore intratumour heterogeneity reveals that intratumor variation is low for most probe sets tested but that multiple biopsies are recommended for reliable estimates of gene expression

Project description:To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor.The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T =W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values.

2007-11-11 | E-GEOD-5787 | biostudies-arrayexpress