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GSE38614
Rattus norvegicus
18 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 2 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To investigate potential differences between strong and weak oscillators at the gene expression level we carried out a transcriptome analysis for each cell line. Our results indicate that phenotypic circadian clock differences are reflected by gene expression differences both in genes of the core network, but also in additional genes not directly associated with circadian clock functions.
Publication Title
Ras-mediated deregulation of the circadian clock in cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A molecular signature of proteinuria in glomerulonephritis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.
Publication Title
A molecular signature of proteinuria in glomerulonephritis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.
Publication Title
A molecular signature of proteinuria in glomerulonephritis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endocapillary proliferation is associated with higher risk of progressive disease in IgAN. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways modulated by corticosteroid exposure. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for treatment of IgAN.
Publication Title
The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
In order to test the hypothesis that fibroblasts from different tissues are phenotypically distinct from one another, we have subjected tendon, skin and corneal fibroblasts of fetal mouse to mechanical stimulation by fluid flow and analyzed the transcriptional responses of the cells using Affymetrix MOE430 chip set containing two arrays MOE430A and MOE430B.
Publication Title
Phenotypic responses to mechanical stress in fibroblasts from tendon, cornea and skin.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human genome-wide Affymetrix GeneChip arrays were used to compare the levels of gene expression in the peripheral blood mononuclear cells (PMBCs) of male patients with post-viral chronic fatigue (n=8) and male healthy control subjects (n=7). Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance. Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.
Publication Title
A gene signature for post-infectious chronic fatigue syndrome.
Sample Metadata Fields
No sample metadata fields
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