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GSE49800
Homo sapiens
36 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
Publication Title
Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
Publication Title
Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue.
Sample Metadata Fields
Sex, Age
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The embryo lethal adenosine methylase tDNA knockout line SALK_074069 was partially complemented with its cDNA driven by the embryo specific ABI3 promoter (A6 lines). The plants have reduced adenosine methylation and show pleiotropic phenotypes. Rosette leaves were harvested from 3 week old plants, both wild-type and mutant plants in triplicate and analysed using the Affymetrix ATH1 array.
Publication Title
Adenosine Methylation in Arabidopsis mRNA is Associated with the 3' End and Reduced Levels Cause Developmental Defects.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
IlluminaHiSeq2500
Description
We compare the performance of two library preparation protocols (poly(A) and exome capture) in in vitro degraded RNA samples Overall design: VcaP cell were grown, and treated with MDV3100 (enzalutamide) or DHT (dihydrotestosterone), intact RNA was isolated and samples were prepared in technical triplicates using two library preparation protocol. Also cells were subject to in vitro degradation through incubation of the whole cell lysate in 37C for increasing amounts of time. Following incbation paired capture and poly(A) libraries were prepared.
Publication Title
The use of exome capture RNA-seq for highly degraded RNA with application to clinical cancer sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Soft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy, with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25-30% response rate in large multi-institutional trials. Although liposarcomas are the most common histological form of adult soft tissue sarcomas, research in this area is severely hampered by the lack of experimentally tractable in vitro model systems. To this end, here we describe a novel in vitro model for human pleomorphic liposarcoma. The cell line (LS2) is derived from a pleomorphic liposarcoma that utilizes Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance, which may be particularly important in modulating the response of this tumor type to DNA damaging agents. We present detailed baseline molecular and genomic data, including genome wide copy number and transcriptome profiles, for this model compared to its parental tumor and a panel of liposarcomas covering multiple histologies. The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor, and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas. We also demonstrate the utility of this model, together with two additional human liposarcoma cell lines, to investigate the relationship between topoisomerase 2A expression and the sensitivity of ALT-positive liposarcomas to doxorubicin. This model, together with its associated baseline data, provide a powerful new tool to develop treatments for this clinically poorly-tractable tumor, and to investigate the contribution that ALT makes to modulating sensitivity to DNA damaging chemotherapeutic agents such as doxorubicin.
Publication Title
Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A gene expression signature purporting to distinguish between telomerase and ALT immortalization has recently been described (Lafferty-Whyte et al., 2009). This was obtained as the intersection of two independent signatures, one obtained from cell lines and the other from a panel of liposarcomas, which utilize different telomere maintenance mechanisms (TMMs). To assess the utility of this signature we used Affymetrix U133plus2.0 arrays to undertake a similar analysis of an independent collection of liposarcomas of defined TMM. In our dataset, the 297 gene signature causes the liposarcomas to cluster not on the basis of TMM, but rather on the basis of tumor histological subtype [Figure 1], consistent with the signatures reported by others (Matushansky et al., 2008).
Publication Title
Validating a gene expression signature proposed to differentiate liposarcomas that use different telomere maintenance mechanisms.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Results: We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary components to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) improve intestinal barrier function, (iii) lower systemic inflammation and (iv) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate improves gut barrier function and reduces atherosclerosis development. Conclusions: Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis. Overall design: Intestinal mRNA profiles of gnotobiotic ApoE KO mice colonized with "core" community or "core plus Roseburia intestinalis" were generated by deep sequencing using Illumina HiSeq.
Publication Title
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were determined in XVE-14 and wild-type seedlings induced for 45 min b-estradiol in order to identify the genes early regulated by EBE transcription factor.
Publication Title
EBE, an AP2/ERF transcription factor highly expressed in proliferating cells, affects shoot architecture in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An integrative analysis of this compendium of proteomic alterations and transcriptomic data was performed revealing only 48-64% concordance between protein and transcript levels. Importantly, differential proteomic alterations between metastatic and clinically localized prostate cancer that mapped concordantly to gene transcripts served as predictors of clinical outcome in prostate cancer as well as other solid tumors.
Publication Title
Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HiSeq 2500
Description
Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a background of chronic inflammation. Dendritic cells (DCs) are potent T-cell stimulators; yet despite DCs' extensive presence in skin, cutaneous T cells in CTCL do not respond with effective anti-tumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3; and CD8+ CTCL populations comprised more T cells expressing CTLA-4 and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell costimulator (ICOS), a marker of T-cell activation. DC émigrés from healthy or CTCL skin biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1 expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA expression profiles corroborated that advanced T3/T4 stage samples expressed higher levels of checkpoint inhibition genes compared with T1/T2 stage patients or healthy controls. Exhaustion of activated T cells is therefore a hallmark of both CD4+ and CD8+ T cells directly isolated from the lesional skin of patients with CTCL, with a continuum of increasing expression in more advanced stages of disease. These results justify identification of antigens driving T-cell exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion earlier in the treatment of CTCL. Overall design: RNA-seq correlated with tumor stages
Publication Title
Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples