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GSE41055
Homo sapiens
27 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity. We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.
Publication Title
A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines.
Publication Title
Multifactorial approach to predicting resistance to anthracyclines.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
We have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by RT-qPCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomirs) among regulated miRNAs. Overall design: Time course experiment comparing HeLa gene expression in response to EGF analyzed by small RNA-seq using Illumina 36-bp read massively parallel sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6h and harvested for RNA extraction. Thus, a total of 6 samples were analyzed, 3 controls and the 3 respective treated counterparts. These same samples were also analyzed in parallel on two different microarray platforms.
Publication Title
Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Epidermal growth factor (EGF) is a key regulatory growth factor activating a myriad of processes affecting cell proliferation and survival that are relevant to normal development and disease. Here we have used a combined approach to study the EGF dependent transcriptome of HeLa cells. We obtained mRNA expression profiles using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, Febit, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer I (GA-I). By applying a procedure for cross-platform data meta-analysis based on rank product and global ancova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We used this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we found a whole new set of genes previously unrelated to the currently accepted EGF associated cellular functions, among which are metallothionein genes. We propose the use of global genomic cross-validation to generate more reliable datasets derived from high content technologies (microarrays or deep sequencing). This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data. Keywords: treated vs. untreated comparison, time course Overall design: Time course experiment comparing HeLa gene expression in response to EGF analyzed on different microarray platforms (Agilent, IMPPC, Illumina, and Operon) and by digital gene expression using short read high throughput tag sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6, and 24 h and harvested for RNA extraction. Technical dye swap duplicates were performed for each of the three biological replicates in both time points. Comparative genomic hybridization of HeLa cell genomic DNA versus poooled genomic DNA from blood obtained from human females conducted on commercial oligonucleotide microarrays (Human Genome CGH Microarray Kit 244A, Agilent Technologies) in order to assess DNA dosage dependence of gene expression levels and response to EGF. Digital gene expression using short read high throughput tag sequencing data submitted to NCBI''s SRA
Publication Title
Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that EGFR is a key mediator in this early activation. To begin to address how this signalling pathway is responsible for the rapid activation of infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a EGFR-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection.
Publication Title
Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).
Publication Title
Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulatory T cells (Treg) are pivotal for the maintenance of peripheral tolerance by controlling self-reactive, chronic and homeostatic T cell responses. We now report that the increase in Treg suppressive function observed in lymphopenic mice correlates with the degree of lymphopenia and is caused by a higher frequency of a novel subpopulation of CD103posICOSpos cells among peripheral Treg that differentially express multiple Treg signature genes.
Publication Title
A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in lymphopenic mice and represents a lymph node specific differentiation stage.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that phosphatidylinositol 3-kinase [PI(3)K] is a key mediator in this activation. To begin to address how this signalling pathway is responsible for the functional changes in infected monocytes, we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes were regulated in a PI(3)K-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection.
Publication Title
PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli k-12
- 18 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
RepA-WH1 is a synthetic bacterial prionoid, i.e., a protein that aggregates as amyloid in bacteria leading to cell death
Publication Title
Outlining Core Pathways of Amyloid Toxicity in Bacteria with the RepA-WH1 Prionoid.
Sample Metadata Fields
Disease, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
microRNAs (miRNAs) regulate virtually all biological processes, but little is known of their role in germinal center (GC) B cells. While the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 functions as a positive modulator of the GC response through the regulation of a DNA repair gene network. Moreover, we show that miR-217 overexpression promotes mature B cell lymphomagenesis. Therefore miR-217 provides a novel molecular link between the normal GC response and B cell transformation Overall design: 4 samples were analyzed by RNAseq: 1) naïve (CD19+Fas-GL7-) B cells from miR-217TG, 2) GC (CD19+Fas+GL7+) B cells from miR-217TG, 3) naïve (CD19+Fas-GL7-) B cells from littermate controls and 4) GC (CD19+Fas+GL7+) B cells from littermate controls. Samples were isolated by cell sorting from pooled Peyer’s patches (4-6 animals per genotype). Two independent experiments were performed.
Publication Title
miR-217 is an oncogene that enhances the germinal center reaction.
Sample Metadata Fields
Specimen part, Subject
View Samples