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SRP126861
Homo sapiens
11 Downloadable Samples
Illumina HiSeq 2500
Description
Background – Epigenetic alterations are stable modifications to chromatin structure that occur in response to environmental cues such as hypoxia or altered nutrient delivery. DNA methylation is a well-established and dynamic DNA modification that contributes to the regulation of gene expression. In the current study, we test the hypothesize that ischemic heart failure is defined by a distinct signature of DNA methylation that corresponds with altered expression of genes involved in cardiac ventricular dysfunction. Methods and Results – Using a methylation array, we quantified genome-wide DNA methylation of endomyocardial samples acquired from patients with ischemic (n = 6) or non-ischemic (n = 5) heart failure. RNA-sequencing analysis was performed in the same samples to identify transcriptomic changes (Fold Change > 1.5, Q < 0.05, FPKM > 2) associated with differential methylation (|Percent Change| > 5%, p < 0.05). Of the promoter-associated CpG Islands, which are well-established regions of negative transcriptional regulation, we identified a signature of robust hypermethylation. The methylation changes linked to significantly decreased transcripts included key fatty acid metabolic regulators (e.g. KLF15, AGPAT9, APOA1, and MXD4). Among the few hypomethylated and induced genes was PFKFB3, which encodes for the rate-limiting enzyme of glycolysis. Gene set enrichment analysis identified TGFß as a nodal upstream regulator of the methylation changes, potentially supporting a role of DNA methylation in the increased fibrosis and apoptosis that accompanies ischemic heart failure. Conclusions – Our data identify that the DNA methylation signature recapitulates the pathologic hallmarks of ischemic heart failure. Furthermore, we show that differential DNA methylation of CpG islands within the promoter depict alterations in metabolic substrate utilization known to occur in ischemic heart failure, and may govern a return to the fetal-like metabolic program. Overall design: RNA Sequencing analysis of left ventricle samples in 11 subjects with end-stage heart failure.
Publication Title
Genome-wide DNA methylation encodes cardiac transcriptional reprogramming in human ischemic heart failure.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.
Publication Title
Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
We used RNA sequencing to identify differentially expressed genes during esophageal epithelial differentiation and in the presence of interleukin 13 using an air-liquid interface culture system. Overall design: RNA sequencing was performed on a human esophageal epithelial cell line (EPC2-hTERT) grown submerged (day 8) or at the air-liquid interface (ALI) (day 14, untreated or treated with interleukin 13 [100 ng/mL])
Publication Title
Eosinophilic esophagitis-linked calpain 14 is an IL-13-induced protease that mediates esophageal epithelial barrier impairment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains that contribute to the viral life cycle, including the DNA binding and helicase domains. In addition, the LT the C-terminal region is required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells and identified interacting cellular proteins and performed expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes.
Publication Title
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In theses experimetns we have analized the differential gene expression profile in human trabecular meshwork cells phagocytically challenged to E. coli and pigment under physiological and oxidative stress conditions using affymetrix microarrays
Publication Title
Up-regulated expression of extracellular matrix remodeling genes in phagocytically challenged trabecular meshwork cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Peripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Publication Title
Transcriptome analysis of early pregnancy vitamin D status and spontaneous preterm birth.
Sample Metadata Fields
Sex, Race
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of this study was to contrast genome-wide gene expression profiles of cultured human trabecular meshwork (HTM) cells, to that of control and primary open angle glaucoma (POAG) HTM tissues.
Publication Title
Genome-wide expression profile of human trabecular meshwork cultured cells, nonglaucomatous and primary open angle glaucoma tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Peripheral whole blood transcriptome profiles of pregnant women enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
Publication Title
The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
Sample Metadata Fields
Sex, Specimen part, Treatment, Race
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina HiSeq 2000
Description
Rationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for primary human airway smooth muscle cell lines from fatal asthma or control donors that were treated with vitamin D, albuterol, or were left untreated.
Publication Title
Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 448 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or passenger and causal, or driver cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. These complementary approaches together result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer.
Publication Title
Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
Sample Metadata Fields
Cell line
View Samples