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accession-icon GSE57633
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigatoing molecular mechanisms of drug resistance
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIllumina HumanWG-6 v3.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.

Sample Metadata Fields

Sex

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accession-icon GSE57491
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigatoing molecular mechanisms of drug resistance (expression)
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIllumina HumanWG-6 v3.0 expression beadchip

Description

Background: Patient-derived tumour xenografts are an attractive model for preclinical testing of anti-cancer drugs. Insights into tumour biology and biomarkers predictive of responses to chemotherapeutic drugs can also be gained from investigating xenograft models. As a first step towards examining the equivalence of epigenetic profiles between xenografts and primary tumours in paediatric leukaemia, we performed genome-scale DNA methylation and gene expression profiling on a panel of 10 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone response. Results: We found high correlations in DNA methylation and gene expression profiles between matching primary and xenograft tumour samples with Pearsons correlation coefficients ranging between 0.85 and 0.98. In order to demonstrate the potential utility of epigenetic analyses in BCPALL xenografts, we identified DNA methylation biomarkers that correlated with prednisolone responsiveness of the original tumour samples. Differential methylation of CAPS2, ARHGAP21, ARX and HOXB6 were confirmed by locus specific analysis. We identified 20 genes showing an inverse relationship between DNA methylation and gene expression in association with prednisolone response. Pathway analysis of these genes implicated apoptosis, cell signalling and cell structure networks in prednisolone responsiveness. Conclusions: The findings of this study confirm the stability of epigenetic and gene expression profiles of paediatric BCP-ALL propagated in mouse xenograft models. Further, our preliminary investigation of prednisolone sensitivity highlights the utility of mouse xenograft models for preclinical development of novel drug regimens with parallel investigation of underlying gene expression and epigenetic responses associated with novel drug responses.

Publication Title

Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.

Sample Metadata Fields

Sex

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accession-icon GSE67158
Eomes+ natural Th1 (nTh1) T cells share functional features with classical Th1 (cTh1) cells.
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Identification of intrathymic Eomes+ natural Th1 cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. To more deeply characterize this type of innate T cells, we compared the gene expression profile between nTh1 cells generated in CIITAtg mice and classic Th1 cells differentiated from naive CD4 T cells in Th1-polarizing condition.

Publication Title

Thymic low affinity/avidity interaction selects natural Th1 cells.

Sample Metadata Fields

Age, Specimen part

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accession-icon SRP012162
Zea mays Transcriptome or Gene expression
  • organism-icon Zea mays
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

This research identifies a novel protein required for paramutation at the maize purple plant1 locus. This 'required to maintain repression2' (RMR2) protein represents the founding member of a plant-specific clade of hypothetical proteins. We show that RMR2 is required for transcriptional repression at the Pl1-Rhoades haplotype, for accumulation of 24 nt RNA species, and for maintenance of a 5-methylcytosine pattern distinct from that maintained by RNA polymerase IV. Genetic tests indicate that RMR2 is not required for paramutation occurring at the red1 locus. These results distinguish the paramutation-type mechanisms operating at specific haplotypes. The RMR2 clade of proteins provides a new entry point for understanding the diversity of epigenomic control operating in higher plants. Overall design: Examination of small RNAs using Illumina's sequencing-by-synthesis (SBS) platform to deep sequence small RNA libraries made from the 4-cm cobs of rmr2 mutant and non-mutant siblings.

Publication Title

required to maintain repression2 is a novel protein that facilitates locus-specific paramutation in maize.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE99018
Ileum Microarray Data from Transcriptomics Driven Lipidomics (TDL) identifies the microbiome-regulated targets of ileal lipid metabolism Study
  • organism-icon Mus musculus
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Microbiome regulation of lipid metabolism

Publication Title

Transcriptomics-driven lipidomics (TDL) identifies the microbiome-regulated targets of ileal lipid metabolism.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP135771
The m 6 A-methylase complex recruits TREX and regulates mRNA export.
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Here we show that the m6A complex (WTAP, KIAA1429, METTL3/14) drives recruitment of the TREX mRNA export complex onto m6A modified mRNAs and this process is essential for the efficient export of certain mRNAs. Depletion of the core m6A complex leads to loss of TREX from mRNAs which undergo the m6A modification. We show that TREX stimulates recruitment of the m6A reader protein YTHDC1 to the mRNP and the m6A complex influences the interaction of TREX with YTHDC1. We suggest that m6A acts as a surrogate for other TREX recruitment mechanisms such as splicing and 5' capping, in long internal and final exons which may otherwise be devoid of this essential complex for mRNA export. Overall design: mRNA profiles of control and Virilizer/WTAP RNAi samples in cytoplasmic and nuclear cell fractions generated by mRNA-seq in triplicate using HiSeq 2500

Publication Title

The m<sup>6</sup>A-methylase complex recruits TREX and regulates mRNA export.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE1428
Skeletal muscle sarcopenia
  • organism-icon Homo sapiens
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

This series includes the global gene expression profile of the vastus lateralis muscle for 10 young (19-25 years old) and 12 older (70-80 years old) male subjects.

Publication Title

Identification of a molecular signature of sarcopenia.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE44671
Wound response in fs-THz-irradiated mouse skin
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NFB1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF- and activation of its downstream target genes, which perturbs the wound healing process in vivo.

Publication Title

High-power femtosecond-terahertz pulse induces a wound response in mouse skin.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE25908
Distinct Protein Degradation Induced by Different Disuse Models of Skeletal Muscle Atrophy
  • organism-icon Mus musculus
  • sample-icon 111 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Skeletal muscle atrophy is a consequence of many diseases, environmental insults, inactivity, age and injury. Atrophy is characterized by active degradation and removal of contractile proteins and a reduction in fiber size. Animal models have been extensively used to identify pathways leading to atrophic conditions. Here we have used genome-wide expression profiling analysis and quantitative PCR to identify the molecular changes that occur in two clinically relevant animal mouse models of muscle atrophy, hindlimb casting and Achilles tendon laceration (tenotomy). Gastrocnemius muscle samples were collected 2, 7 and 14 days after insult. The total amount of muscle loss as measured by wet weight and muscle fiber size was equivalent between models, although tenotomy resulted in a more rapid induction of muscle atrophy. Furthermore, tentomy resulted in the regulation of significantly more mRNA transcripts then casting. Analysis of the regulated genes and pathways suggest that the mechanism of atrophy is distinct between these models. The degradation following casting appears ubiquitin-proteasome-mediated while degradation following tenotomy appears lysosomal and matrix-metalloproteinase (MMP)-mediated. This data suggests that there are multiple mechanisms leading to muscle atrophy and that specific therapeutic agents may be necessary to combat the atrophy seen under different conditions.

Publication Title

Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy.

Sample Metadata Fields

Sex, Specimen part, Treatment, Time

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accession-icon SRP181663
Next Generation Sequencing Quantitative Analysis of HepG2, hyper-glycolytic model cell, oxamate treated cells
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

To determine the genes potentially responsible for the lactate-mediated gene expression regulation in hepatocellular carcinoma, we performed RNA-seq analyses on parental HepG2, HepG2/metR and oxamate-treated HepG2/metR cells. To gain mechanistic insights into the lactate-induced pro-migratory phenotypes, we established a cell model that acquired a resistance to metformin while producing lactate at a high level by selecting HepG2 cells that survived a chronic exposure to metformin for more than 5 months (HepG2/metR). In HepG2/metR cells, glycolysis rates were increased by more than 3 folds compared with parental cells, and consequently, lactate production was also highly enhanced. To clarify the gene expression regulation between the lactate level in the HepG2/metR model, we treated the cells with oxamate, an inhibitor of lactate dehydrogenase, and found that it significantly. Using a 2-fold change cut-off value in transcriptome, we selected 1,757 genes significantly up-regulated in HepG2/metR vs parental HepG2 cells. 690 genes were down-regulated by oxamate treatment in HepG2/metR cells. Eventually, we selected 136 genes that are common in the two gene sets, which may directly respond to lactate signaling Overall design: mRNA profiles of HepG2 cells, HepG2/metR (hyper-glycolytic cell model), oxamate treated HepG2/metR (decreased lactate concentration cell) were generated by deep sequencing using Illumina Nextseq 500

Publication Title

Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes.

Sample Metadata Fields

Specimen part, Cell line, Treatment, 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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