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GSE68761
Homo sapiens
74 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from downstream effects of pathway perturbations. To date, Nested Effect Models cannot resolve signalling details like the formation of signalling complexes or the activation of proteins by multiple alternative input signals. Here we introduce Boolean Nested Effect Models (B-NEM). B-NEMs combine the use of downstream effects with the higher resolution of signalling pathway structures in Boolean Networks. We show that B-NEMs accurately reconstruct signal flows in simulated data. Using B-NEM we then resolve BCR signalling via PI3K and TAK1 kinases in BL2 lymphoma cell lines.
Publication Title
Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The epithelial to mesenchymal transition (EMT) of malignant hepatocytes is a crucial event in hepatocellular carcinoma (HCC) progression and recurrence. We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. Human HCC cell populations were characterized by immunofluorescence analysis, migration and invasion assays, array comparative genomic hybridization, whole-genome expression profiling and promoter methylation. Therapeutic agents clinically used against HCC were examined for efficacy by determination of IC50 values. Liver cancer cell lines showed either an epithelial or mesenchymal phenotype of which latter showed strong migratory and invasive abilities in vitro. The common cellular origin of both cell types indicated that mesenchymal HCC cells have been derived from epithelial hepatocytes through EMT in the HCC patient. Drug exposure of mesenchymal HCC cells showed higher resistance to the targeted therapeutic agents sorafenib and erlotinib as compared to epithelial HCC cells, which were slightly more resistant to cytostatic drugs. Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. Taken together, this novel model of human HCC allows to monitor the differential effect of liver cancer progression on drug efficacy in pre-clinical studies.
Publication Title
A human model of epithelial to mesenchymal transition to monitor drug efficacy in hepatocellular carcinoma progression.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
PcG protein complex PRC2 is a methyltransferase specific for histone H3 lysine27, and H3K27me3 is essential for stable transcription silencing. Less well known but quantitatively much more important is the genome-wide role of PRC2 that dimethylates ~70% of total H3K27. Here we show that H3K27me2 occurs in inverse proportion to transcriptional activity in genes and intergenic regions and its loss results in global transcriptional derepression proportionally greatest in previously silent or weakly transcribed regions. H3K27me2 levels are controlled by opposing roaming activities of PRC2 and the H3K27 demethylase dUTX. Unexpectedly, we find an equally pervasive distribution of histone H2A ubiquitylated at lysine 118 (H2AK118ub), attributed to the RING1 subunit of PRC1-type complexes. Overall design: Examination of global changes in transcription genome-wide when E(z) is inactivated by monitoring total RNA from E(z) temperature-sensitive cells at 25°C and 31°C in duplicate
Publication Title
Genome-wide activities of Polycomb complexes control pervasive transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Tip60 is a key histone acetyltransferase (HAT) enzyme that plays a central role in diverse biological processes critical for general cell function, however the chromatin-mediated cell-type specific developmental pathways that are dependent exclusively upon the HAT activity of Tip60 remain to be explored. Here, we investigate the role of Tip60 HAT activity in transcriptional control during multicellular development, in vivo by examining genome-wide changes in gene expression in a Drosophila model system specifically depleted for endogenous dTip60 HAT function. We show that amino acid residue E431 in the catalytic HAT domain of dTip60 is critical for the acetylation of endogenous histone H4 in our fly model in vivo, and demonstrate that dTip60 HAT activity is essential for multicellular development. Moreover, our results uncover a novel role for Tip60 HAT activity in controlling neuronal specific gene expression profiles essential for nervous system function as well as a central regulatory role for Tip60 HAT function in general metabolism.
Publication Title
Microarray analysis uncovers a role for Tip60 in nervous system function and general metabolism.
Sample Metadata Fields
Specimen part
View Samples- Equus caballus
- 13 Downloadable Samples
- Equus caballus Gene 1.0 ST Array (equgene10st)
Description
Alveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Publication Title
Comparative transcriptome analysis of equine alveolar macrophages.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
Comparison of R1 embryonic stem cells response to DMSO and retinoic acid and control
Publication Title
Meta-analysis of differentiating mouse embryonic stem cell gene expression kinetics reveals early change of a small gene set.
Sample Metadata Fields
Specimen part, Cell line, Compound
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
Publication Title
Genome-wide analysis of Polycomb targets in Drosophila melanogaster.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To try to investigate the mechanism behind the adaptive phenotypes observed in a mice model model of HD crossed with mGluR5 knockout, we analyzed whether mutated huntingtin (Htt) expression in a mGluR5 null background could be altering the expression of genes that might be involved in the pattern of Htt aggregation and HD-related locomotor alterations.
Publication Title
Metabotropic glutamate receptor 5 knockout promotes motor and biochemical alterations in a mouse model of Huntington's disease.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina Genome Analyzer II
Description
We evaluated the trancriptome of primary cutaneous leisions caused by infection with Leishmania braziliensis. mRNA-seq technique was used to study the trancriptome of both host and parasite. A total of 10 samples was obtained from primary skin ulcers of two extreme clinical forms of American tegumentary leishmaniasis: (i) individuals that after antimonial treatment cured completely (localized cutaneous leishmaniasis - LCL, n=5) and (ii) individuals that developed mucosal lesions in naso and oropharynx areas long after initial healing of the cutaneous lesion (mucosal leishmaniasis - ML, n=5). The sequencing generated an average of 13+ 5 million reads per samples. The reads were aligned to Homo sapiens (USCS - hg19) and to Leishmania braziliensis (Wellcome Trust Sanger Institute - V2_29072008) genomes. Approximately, 15,000 human genes could be detected in the samples. Low amount of L. braziliensis reads did not allow the evaluation of parasite gene expression. LCL and ML samples showed different patterns of gene expression, indicating a more robust immune response in LCL individuals. In summary, this study demonstrated that next-generation sequencing can be used for identification of potentially important biological pathways and drug targets in the host-response to L. braziliensis infection and for characterization of a gene expression signature that could be used to predict the disease outcome. Moreover, we also showed the ability of this technique in, simultaneously, sequence host and pathogen mRNA. Overall design: Examination of 10 fragments of cutaneous lesions: 5 from localized cutaneous leishmaniasis patients and 5 from mucosal leishmaniasis patients.
Publication Title
Transcriptome patterns from primary cutaneous Leishmania braziliensis infections associate with eventual development of mucosal disease in humans.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Activated pancreatic stellate cells produce the fibrotic matrix in chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a non-physiological surface. However, PSCs cultured on physiological matrices e.g. MatrigelTM (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviours compared to cells cultured on plastic. Therefore, we aimed to compare PSC gene expression after culture on plastic, MatrigelTM and collagen I.
Publication Title
Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function.
Sample Metadata Fields
Sex
View Samples