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GSE107392
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor / cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
Publication Title
Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
T lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
Publication Title
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
T lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
Publication Title
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
Illumina HiSeq 2500
Description
We sought to determine differences in transcript expression between a cohort of HIV-infected individuals that either developed broadly neutralizing antibodies (bnAb) or did not develop them (control). With the ultimate goal to identify transcripts that are associated with the development of bnAbs that would identify novel pathways that could be targeted in future vaccine strategies to increase the frequency of individuals that develop bnAbs against HIV. Using this approach we identified that Rab11 recycling endosomes, particularly in dysfunctional natural killer cells are associated with the development of HIV-1 bnAbs. Overall design: RNA extracted from peripheral blood mononuclear cells of 95 subjects was subject to RNA-seq for transcriptome analysis comparing individuals that developed HIV-1 broadly neutralizing antibodies to those that did not develop them (control).
Publication Title
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Macaca mulatta
- 64 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 34 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 30 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans.
Publication Title
Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 66 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 8.9). Tumors were classified as low (mean = 0.5 0.6, n = 11), medium (mean = 5.4 2.4, n = 10), or high (mean = 19.2 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples