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GSE46914
Homo sapiens
23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The rapid development in septic patients of features of marked immunosuppression associated with increased risk of nosocomial infections and mortality represents the rational for the initiation of immune targeted treatments in sepsis. However, as there is no clinical sign of immune dysfunctions, the current challenge is to develop biomarkers that will help clinicians identify the patients that would benefit from immunotherapy and monitor its efficacy. Using an in vitro model of endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-). These results were confirmed by qRT-PCR. Importantly, this short-list of markers was further evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1, CXCL5 and PID1) were differentially expressed in septic shock patients blood compared to healthy blood upon ex vivo LPS stimulation and were restored by IFN-. In this study, by combining a microarray approach in an in vitro model and a validation in clinical samples, we identified a panel of six transcripts that could be used for the identification of septic patients eligible for IFNg therapy. The potential value of these markers should now be evaluated in a larger cohort of patients. Upon favorable results, they could serve as stratification tools prior to immunostimulatory treatment and to monitor drug efficacy.
Publication Title
Identification of biomarkers of response to IFNg during endotoxin tolerance: application to septic shock.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Publication Title
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Publication Title
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sample Metadata Fields
Sex, Age, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays.
Publication Title
Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 63 Downloadable Samples
Illumina HiSeq 2000
Description
As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes. Overall design: mRNA-sequencing of Drosophila neuron-specific knockdown model heads for six 16p11.2 homologs and wild-type control. Sequencing was performed using Illumina HiSeq 2000 on three biological replicates per sample, with three technical replicates per biological replicate.
Publication Title
Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The human C-type lectin Reg3a (HIP/PAP) is an antimicrobial peptide that kills Gram-positive bacteria. Reg3a preserves gut microbiota homeostasis, reinforces intestinal barrier function and thereby helps to fight induced colitis in mice.
Publication Title
Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Inflammatory bowel diseases (IBD) in humans are characterized by chronic inflammation and gastrointestinal tissue damage, caused by a combination of genetic and environmental factors. It has been largely documented that IBD frequently lead to colorectal cancers (CRC). The identification of causative factors of IBD is thus essential to understand CRC progression and develop therapeutical approaches. Models have been described in which molecular alterations are combined with inflammatory treatments in order to recapitulate IBD-associated CRC. Here, we describe a mouse line, 6fl/fl Villin-Cre, in which inactivation of the gene encoding the integrin alpha-6 subunit (ITGA6) specifically in the intestinal mucosa results into chronic inflammation and intestinal carcinogenesis. In these mice, the loss of integrin alpha-6 beta-4, a receptor mediating the attachment of epithelial cells to laminins, leads to epithelial detachment, hyperplasia, chronic inflammation, rectal prolapses, and ultimately adenocarcinomas. Alterations of differentiation affecting mucus secreting (goblet) cells as well as changes in expression of essential intestinal transcription factors were detected. Thus alpha-6 beta-4 integrin is a key factor for the maintenance of intestinal integrity and its loss may represent a risk factor for tumor progression associated with IBD.
Publication Title
Hemidesmosome integrity protects the colon against colitis and colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of mRNAs extracted from the rectal mucosa of WT and 6IEC-TAM mice, 15 days after tamoxifen treatment
Publication Title
Hemidesmosome integrity protects the colon against colitis and colorectal cancer.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative splicing of pre-mRNA generates protein diversity and has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantication of expression levels for the majority of exons and facilitates the discovery of alternative splicing events. Analysis of exon array data is more challenging than gene expression data and there is a need for reliable quantication of exons and alternative spliced variants. We introduce a novel, computationally efficient methodology, MEAP, for exon array data preprocessing, analysis and visualization. We compared MEAP with other preprocessing methods, and validation of the results show that MEAP produces reliable quantication of exons and alternative spliced variants. Analysis of data from head and neck squamous cell carcinoma (HNSCC) cell lines revealed several variants associated with 11q13 amplication, which is a predictive marker of metastasis and decreased survival in HNSCC patients. Together these results demonstrate the utility of MEAP in suggesting novel experimentally testable predictions. Thus, in addition to novel methodology to process large-scale exon array data sets, our results provide several HNSCC candidate genes for further studies.
Publication Title
Comprehensive exon array data processing method for quantitative analysis of alternative spliced variants.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Wild type Columbia and serrate-1 globular stage embryos were sequenced in order to profile miRNAs which are expressed in embryogenesis in Arabidopsis thaliana Overall design: Two biological replicates, two conditions
Publication Title
Arabidopsis thaliana miRNAs promote embryo pattern formation beginning in the zygote.
Sample Metadata Fields
Specimen part, Subject
View Samples