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GSE87382
Homo sapiens
24 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
High MC-SFA intake resulted in a downregulation of gene expression of pathways related to complement system and inflammation, and an upregulation of gene expression of pathways related to citric acid cycle, electron transport chain and lipid metabolism in adipose tissue. Based on our results, we hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation may be mediated by increases in gene expression related to energy metabolism in the adipose tissue. Additionally, decreases in inflammation-related gene expression in the adipose may potentially have beneficial effects in relation to cardiometabolic diseases.
Publication Title
Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The whole blood was collected pre-treatment from rheumatoid arthritis patients starting the anti_TNF therapy. All patients were nave to anti_TNFs. The disease activity was measured using the DAS28 score at the pre-treatment visit1 (DAS28_v1) and 14 weeks after treatment visit3 (DAS28_v3). The response to the therapy was evaluated using the EULAR [European League Against Rheumatism] definition of the response. The objective of the data analysis was to identify gene expression coorelating with response as well as to identify genes that differentiate responders versus non-responders pre-treatment. The results of this investigation identified 8 trainscripts that predict responders vs. non-responders with 89% accuracy.
Publication Title
Convergent Random Forest predictor: methodology for predicting drug response from genome-scale data applied to anti-TNF response.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 25 Downloadable Samples
IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation and translation. We have developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing (Baltz and Munschauer et al. 2012). Our current work focuses on streamlining and extending protein occupancy profiling on poly(A)-RNA. Our objectives are to identify previously unknown protein-bound transcripts and, more importantly, to assess global and local differences in protein occupancy across different biological conditions. To this end, we have implemented poppi, the first pipeline for differential analysis of protein occupancy profiles. We have applied our analysis pipeline to pinpoint changes in occupancy profiles of MCF7 cells against already published HEK293 cells [GSE38157]. Overall design: We generated protein occupancy cDNA libraries for two biological replicates. Briefly, we crosslinked 4SU-labeled MCF7 cells and purified protein-mRNA complexes using oligo(dT)-beads. The precipitate was treated with RNAse I to reduce the protein-crosslinked RNA fragments to a length of about 30-60 nt. To remove non-crosslinked RNA, protein-RNA complexes were precipitated with ammonium sulfate and blotted onto nitrocellulose. The RNA was recovered by Proteinase K treatment, ligated to cloning adapters, and reverse transcribed. The resulting cDNA libraries were PCR-amplified and next-generation sequenced.
Publication Title
Differential protein occupancy profiling of the mRNA transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
RNA helicases are important regulators of gene expression that act by remodeling RNA secondary structures and as RNA-protein interactions. Here, we demonstrate that MOV10 has an ATP-dependent 5'' to 3'' in vitro RNA unwinding activity and determine the RNA-binding sites of MOV10 and its helicase mutants using PAR-CLIP. We find that MOV10 predominantly binds to 3'' UTRs upstream of regions predicted to form local secondary structures and provide evidence that MOV10 helicase mutants are impaired in their ability to translocate 5'' to 3'' on their mRNA targets. MOV10 interacts with UPF1, the key component of the nonsense-mediated mRNA decay pathway. PAR-CLIP of UPF1 reveals that MOV10 and UPF1 bind to RNA in close proximity. Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10-bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in UPF1-mediated mRNA degradation as an RNA clearance factor to resolve structures and displace proteins from 3'' UTRs. Overall design: Flp-In T-REx HEK293 cells expressing FLAG/HA-tagged MOV10 WT, MOV10 K530A, MOV10 D645N and UPF1 were used to determine the protein-RNA interaction sites of RNA helicases MOV10 and UPF1 as well as MOV10 inactive variants using PAR-CLIP in combination with next generation sequencing. mRNA half-life changes of MOV10-targeted mRNA were determined by measuring mRNA half-lives by mRNA sequencing of mock and MOV10-depleted HEK293 cells.
Publication Title
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An Hodgkin Lymphoma cell line have been treated with an LNA inhibitor for miR-9 or with a scramble LNA to identify miR-9 regulated pathways that could be important for Hodgkin Lymphoma pathogenesis.
Publication Title
Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
These data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line.
Publication Title
Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene segregates with most autoimmune diseases; its risk allele encodes overactive PTPN22 phosphatases that alter B cell receptor (BCR) signaling potentially involved in the regulation of central B cell tolerance. To assess whether PTPN22 risk allele affects the removal of developing autoreactive B cells, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from asymptomatic healthy individuals carrying one or two PTPN22 risk allele(s). We found that new emigrant/transitional and mature naive B cells from PTPN22 risk allele carriers contained high frequencies of autoreactive clones compared to non-carrier control donors. Hence, a single PTPN22 risk allele has a dominant effect on altering autoreactive B cell counterselection, suggesting that early B cell tolerance checkpoint defects precede the onset of autoimmunity. In addition, gene array experiments comparing mature nave B cells from healthy individuals carrying or not PTPN22 risk allele(s) revealed that the strength of association of PTPN22 for autoimmunity, second in importance only to the MHC, may not only be due to BCR signaling alteration but also to the regulation of other genes, which themselves have also been identified as involved in the development of autoimmune diseases.
Publication Title
The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
Connections between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established however, the underlying mechanisms remain poorly understood. Here we used a mutant version of elongation factor TFIIS (TFIISmut) to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. TFIISmut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII. It affects mRNA splicing and termination as well. Remarkably, however, TFIISmut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed new light on the relationship between transcription stress and R-loops, and suggest that different classes of R-loops exist, potentially with distinct consequences for genome instability. Overall design: To study RNAPII backtracking and its effects in human cells, we used HEK293 TREX cells in which we overexpressed, under the control of a dox-promoter, a dominant negative form of TFIIS (TFIIS mut), an elongation factor necessary for stimulating RNAPII intrinsic cleavage activity. TFIISmut cells were maintained in the presence of Dox to ensure over-expression for 48 hours prior to harvest..
Publication Title
Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina Genome Analyzer IIx
Description
Circular RNAs (circRNAs) in animals are an enigmatic class of RNAs with unknown function. To systematically explore circRNAs, we sequenced and computationally analyzed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, with oftentimes tissue/developmental stage specific expression. Sequence analysis suggested important regulatory functions for circRNAs. Indeed, we discovered that human circRNA CDR1as is densely bound by miRNA effector complexes and harbors 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebra fish impaired midbrain development similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, indicating previously unrecognized regulatory potential of coding sequences. Overall design: 1 Sample
Publication Title
Circular RNAs are a large class of animal RNAs with regulatory potency.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors, we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. To further characterize this combination, global transcriptomic analysis was performed in A375 and 16R6-4 after 24 hour treatment with GSK2118436, GSK1120212 or the combination of GSK2118436 and GSK1120212.
Publication Title
Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples