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accession-icon GSE19197
Hypoxia modulates EWS-FLI1 transcriptional signature and enhances malignant properties of Ewings tumor cells in vitro
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Hypoxia is an important condition in the tumor cell microenvironment and approximately 1-1.5% of the genome is transcriptionally responsive to hypoxia with hypoxia-inducible factor-1 (HIF-1) as a major mediator of transcriptional activation. Tumor hypoxia is associated with a more aggressive phenotype of many cancers in adults, but data on pediatric tumors are scarce. By immunohistochemical analysis, HIF-1 expression was readily detectable in 18/28 primary Ewings sarcoma family tumors (ESFT), a group of highly malignant bone-associated tumors in children and young adults, which encouraged us to study the effect of hypoxia on ESFT cell lines in vitro.

Publication Title

Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant properties of Ewing's sarcoma cells in vitro.

Sample Metadata Fields

Disease, Cell line

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accession-icon GSE10522
Expression data of Arabidopsis thaliana rosettes during chilling
  • organism-icon Arabidopsis thaliana
  • sample-icon 21 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

To investigate the response of Arabidopsis thaliana plants to non-freezing, cool temperatures, we subjected four week old plants to various chilling temperatures at defined times during the diurnal cycle to control for diurnal effects on transcription. From the same plants, metabolites and enzyme activities were measured as well. Interestingly a gradual change could be observed over a wide range of temperatures. Some of which could be attributed to the CBF program.

Publication Title

Multilevel genomic analysis of the response of transcripts, enzyme activities and metabolites in Arabidopsis rosettes to a progressive decrease of temperature in the non-freezing range.

Sample Metadata Fields

Specimen part

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accession-icon GSE147160
Transcriptomic analysis of amp1-13 and cyp78a5,7 Arabidopsis seedlings
  • organism-icon Arabidopsis thaliana
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

ALTERED MERISTEM PROGRAM1 (AMP1) is a member of the M28 family of carboxypeptidases with a pivotal role in cell fate maintenance in the embryo and shoot meristem. A defect in AMP1 function results in suspensor to embryo conversion and a hypertrophic shoot meristem forming ectopic stem cell pools. However, so far the role of AMP1 in shoot development could not be assigned to a specific molecular pathway nor is its biochemical function resolved. Double mutants in CYP78A5 and CYP78A7 develop a similar set of cell fate defects. To further assess whether this phenotypic overlap is also depicted in a congruency at the global gene expression level, we analyzed the transcriptomic responses of both genotypes

Publication Title

AMP1 and CYP78A5/7 act through a common pathway to govern cell fate maintenance in Arabidopsis thaliana.

Sample Metadata Fields

Age, Specimen part

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accession-icon SRP043115
Upf2 in NMD pathway
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIon Torrent Proton

Description

Purpose: Probe the transcriptome-wide changes in the expression pattern between WT and Sertoli-specific Upf2 KO testes Methods: Total RNA were extracted from WT and Sertoli-specific Upf2 KO testes in triplicates and subject to deep-sequencing in Ion Torrent seq platform. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 16,014 transcripts in the retinas of WT and Nrl-/- mice with BWA workflow and 34,115 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl-/- retina, with a fold change =1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling. Conclusions: Our study represents the first detailed analysis of Upf2-mediated NMD pathway in Sertoli cell development Overall design: Testis mRNA profiling was generated from postnatal day 4 WT and Amh-cKO (Sertoli specific Upf2 KO) testes, in triplicates.

Publication Title

UPF2, a nonsense-mediated mRNA decay factor, is required for prepubertal Sertoli cell development and male fertility by ensuring fidelity of the transcriptome.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE47813
Pre-leukemic Cebpa mutant myeloid progenitors
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

In this study, we use pre-malignant cells from different Cebpa mutant acute myeloid leukemia (AML) models. We have used conditional KO models (CreLoxP) and isolated hematopoietic cells shortly after induction of recombination, in order to look at pre-leukemic cells, which have acquired the first hit, but not yet undergone full malignant transformation.

Publication Title

Lack of the p42 form of C/EBPα leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP038144
UPF2 establishes testis-specific transcriptome enriched in transcripts with shorter 3’UTRs
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

This report not only adds a novel mechanism to the current dogma on achieving global shortening of 3''UTRs, but also unveils a novel function of the NMD pathway in establishing tissue-specific transcriptome identity Overall design: We first generated prospermatogonia-specific Upf2 conditional knockout mice (Ddx4-Cre; Upf2 fl/?, hereafter called Ddx4-KO) by crossing Ddx4-Cre13 with Upf2 floxed.

Publication Title

UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE49975
Integrative analysis of histone ChIP-seq and gene expression microarray data using Bayesian mixture models
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Histone modifications are a key epigenetic mechanism to activate or repress the expression of genes. Data sets of matched microarray expression data and histone modification data measured by ChIP-seq exist, but methods for integrative analysis of both data types are still rare. Here, we present a novel bioinformatic approach to detect genes that are differentially expressed between two conditions putatively caused by alterations in histone modification. We introduce a correlation measure for integrative analysis of ChIP-seq and gene expression data and demonstrate that a proper normalization of the ChIP-seq data is crucial. We suggest applying Bayesian mixture models of different distributions to further study the distribution of the correlation measure. The implicit classification of the mixture models is used to detect genes with differences between two conditions in both gene expression and histone modification. The method is applied to different data sets and its superiority to a naive separate analysis of both data types is demonstrated. This GEO series contains the expression data of the Cebpa example data set.

Publication Title

Integrative analysis of histone ChIP-seq and transcription data using Bayesian mixture models.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE46534
Development of MLL-rearranged leukemia is dependent on a transcriptional program orchestradt by C/EBP
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBP to be up-regulated in the AML samples, suggesting that C/EBP might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBP activity both in early progenitors as well as in GMPs. In contrast, C/EBP was found to be indispensable in an already established leukemia. These results suggest that C/EBP play an important role in the early transforming event of leukemogenesis.

Publication Title

Initiation of MLL-rearranged AML is dependent on C/EBPα.

Sample Metadata Fields

Specimen part

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accession-icon GSE111865
Gene expression Analysis of wild type (WT) and Blnc1 adipose specific transgenic mice (Tg) epididymal WAT (eWAT) Transcriptomes after 21 weeks high fat diet (HFD) feeding
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.1 ST Array (mogene21st)

Description

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health.

Publication Title

The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.

Sample Metadata Fields

Sex, Age, Specimen part, Treatment

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accession-icon SRP144520
The splicing factor RBM25 controls MYC activity in Acute Myeloid Leukemia
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome. Overall design: Examined transcriptome from U937 cells in biological triplicates.

Publication Title

The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.

Sample Metadata Fields

Specimen part, Cell line, Subject

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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