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SRP140515
Homo sapiens
24 Downloadable Samples
NextSeq 500
Description
Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) with asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthma is unclear. Objective: To explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthma. Methods: Primary human bronchial epithelial cell (HBEC) air-liquid interface (ALI) cultures were stimulated with IL-6 and sIL-6R to establish an IL-6TS gene signature. Two separate RNA sequencing (RNA-seq) studies were performed: The “IL-6 vs T2 study” compared gene expression after stimulation with control medium, IL-6, IL-6/sIL-6R and IL-4/IL-13, while the “JAK1-inhibition study” addressed the effect of JAK1 inhibition on IL-6TS induced gene expression. The IL-6TS gene signature was used to stratify lung epithelial transcriptomic data obtained from asthmatics (n=103) in the U-BIOPRED cohorts by hierarchical clustering. Molecular phenotyping was based on the transcriptional profiling of epithelial brushings, pathway analysis and immunohistochemistry analysis of bronchial biopsies. Results: Activation of IL-6TS in HBEC ALI cultures reduced epithelial barrier function and induced a specific epithelial gene signature enriched in airway remodeling genes. The IL-6TS signature identified a subset (n=17) of IL-6TS High asthma patients with increased epithelial expression of IL-6TS inducible genes in absence of increased systemic levels of IL-6 and sIL-6R. The IL-6TS High subset had an increased exacerbation frequency (p=0.028), blood (>300/µl; p=0.0028) and sputum (>20%; p=0.007) eosinophilia, and submucosal infiltration of CD4 T cells, CD8 T cells (p<0.001) and macrophages (p=0.001). In bronchial brushings, TLR pathway genes were up-regulated while the expression of epithelial tight junction genes was reduced (all with q<0.05). Sputum sIL-6R levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, MMP3, IL-8 and IL-1ß (all with q<0.001). Conclusions: Local lung epithelial IL-6TS activation in absence of type 2 airway inflammation defines a novel subset of asthmatics and may drive airway inflammation and epithelial dysfunction in these patients. Overall design: Primary human bronchial epithelial cells grown and differentiated on air-liquid interface were stimulated basolaterally for 24h with cytokines corresponding to IL-6TS (IL-6 + sIL-6R), IL-6 alone, a Type 2 immune response (IL-4 + IL-13) or media alone as non-stimulated control. Each stimulation condition was done in triplicates. Cells were lysed, the RNA isolated and converted into libraries then used for next generation sequencing in order to identify genes that were up- or downregulated in response to the different stimulations.
Publication Title
Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 839 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 459 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Publication Title
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 233 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Publication Title
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 147 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Genome-wide analysis of transcriptional profiles in children <17 years of age with inflammatory diseases, bacterial or viral infections or with clinical features suggestive of infection.
Publication Title
Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
The Adar1 deaminase inactive mutant mouse tissue samples were obtain from the Walkley lab as described in http://www.ncbi.nlm.nih.gov/pubmed/26275108. We performed mmPCR-seq on the samples and measured the editing levels of. Overall design: Fetal mRNA profiles of E12.5 wild type (WT) and ADAR E861A mutant mice were generated by deep sequencing using Illumina HiSeq 2000.
Publication Title
Dynamic landscape and regulation of RNA editing in mammals.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) relates to inferior survival in multiple myeloma (MM). MRD PCs are therefore a minor clone able to recapitulate the initial tumor burden at relapse and accordingly, its characterization may represent a unique model to understand chemoresistance; unfortunately, the MRD clone has never been biologically investigated. Here, we compared the antigenic profile of MRD vs. diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study, and showed that the MRD clone is enriched by cells over-expressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4) and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs. diagnostic PCs showed identical copy number alterations (CNAs) in 3/8 cases, 2 patients with linear acquisition of additional CNAs in MRD clonal PCs, and 3 cases with variable acquisition and loss of CNAs over time. The MRD clone showed significant downregulation of genes particularly related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and identifies chemoresistant PCs in vitro. Together, we show that therapy-induced clonal selection is already present at the MRD stage, in which chemoresistant PCs show a specific phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Publication Title
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Despite the benefits associated with healthy diets, data on the mechanisms by which these benefits are promoted are scarce. Our aim was to explore the global transcriptomic response of biological pathways related to cardiovascular disease associated with traditional Mediterranean diet (TMD) intervention. The PREDIMED study is a large on-going, parallel, multicentre, randomised, controlled trial aimed at assessing the TMD effect on primary cardiovascular prevention. High cardiovascular risk participants were recruited and assigned to one of the following interventions: 1) TMD plus virgin olive oil (VOO); 2) TMD plus mixed nuts; or 3) low-fat diet (control group). In a sub sample of 30 volunteers of the PREDIMED- Barcelona Sur Centre, gene expression changes in peripheral mononuclear cells, after 3 months of intervention, were assessed by microarray analysis.
Publication Title
In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: a randomized controlled trial.
Sample Metadata Fields
Time
View Samples