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accession-icon SRP179098
Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos
  • organism-icon Danio rerio
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Purpose: the goal of this project is to study the effects of the PFOS (perfluorooctanesulfonate) in the transcriptome profiling (RNA-seq) of exposed zebrafish larvae. Methods: Total RNA was isolated from the samples using AllPrep DNA/RNA Mini Kit (Qiagen, CA, USA) as described by the manufacturer. Three high quality sample per condition were chosen to the mRNA enrichment using KAPA Stranded mRNA-Seq Kit Illumina® Platforms (Kapa Biosystems). Transcriptomic profiles were generated by deep sequencing using Illumina TruSeq SBS Kit v3-HS (pair-ended; 2x76bp) on a HiSeq2000 sequencing system. Image analysis, base calling and quality scoring of the run were processed using the manufacturer's software Real Time Analysis (RTA 1.13.48) and followed by generation of FASTQ sequence files by CASAVA. Statistical analysis: RNA-seq reads were aligned to the D. rerio reference genome (GRCz10) using STAR version 2.5.1b . Genes annotated in GRCz10.84 were quantified using RSEM version 1.2.28 with default parameters. Differential expression analysis between all PFOS conditions was performed with the DESeq2 (v.1.10.1) R package with the Likelihood ratio test option. ANOVA-PLS was performed on the normalized data using the lmdme package in R (v. 1.0.136, R Core Team). Results: We generated on average 39 million paired-end reads for each sample and identified aproximatelly 24500 transcripts. 1434 differentially expressed genes (DEGs) were detected which could be divided in 2 clusters including 767 and 667 genes, respectively. Affected metabolic pathways were analyzed from the DEGs: lipid transport and metabolism, protein ubiquination, antigen processing, immune system, apoptosis, trans-membrane, cell matrix, Zn-ion binding, cytokines and JAK-STAT signaling pathways', among others, were down or upregulated. Conclusions: Our results suggest a complex, multiple endocrine disruption-like toxic effects at a concentrations well bellow the 1 mg/L, considered as the LOAEC/NOAEC for many of the macroscopic effects traditionally linked to PFOS toxicity in zebrafish embryos. While our results confirm the known effect of PFOS in lipid metabolism, we found a clear decrease on expression of many genes related to natural immunity and defense against infections. We propose that this transcriptional pattern may be a marker for the immunotoxic effects of PFOS and other related substances in fish and other vertebrates, including humans. We concluded that our analysis allowed us the identification of underlying molecular mechanisms occurring simultaneously at the exposed animals. While this approach is very useful to analyze the effects of compounds, like PFOS, able to interact with different cellular targets, we believe that it can be also applied to the characterization of the different toxic components present in complex natural mixtures. Overall design: Whole embryo (5 dpf; wild type zebrafish) mRNA profiles of 4 groups (control, 0.03, 0.3 and 1 ppm of PFOS) were generated by deep sequencing, in triplicate, using Illumina TruSeq SBS Kit v3-HS (pair-ended) on a HiSeq2000 sequencing system.

Publication Title

Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos.

Sample Metadata Fields

Age, Subject

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accession-icon SRP140620
Transcriptomic analysis of A. thaliana roots in response to carbenicillin
  • organism-icon Arabidopsis thaliana
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

A. thaliana plants were grown in 1/2 MS medium in the presence of carbenicillin (10 µg·mL-1) for 1 or 7 days and RNA from their roots extracted and sequenced in Illumina HiSeq 2000/5000 (2x50 bp). Overall design: Total RNA obtained from A. thaliana roots grown in the absence (mock) or presence of carbenicillin (10 µg·mL-1) for 1 or 7 days. Three replicas per experiment.

Publication Title

β-Lactam Antibiotics Modify Root Architecture and Indole Glucosinolate Metabolism in Arabidopsis thaliana.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE108033
Maternal gene expression data from dMLL3/4-depleted Drosophila embryos
  • organism-icon Drosophila melanogaster
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Drosophila Gene 1.1 ST Array (drogene11st)

Description

Analysis of Drosophila melanogaster early embryos (pre-zygotic genome activation) following the germ line-specific depletion of the dMLL3/4 histone methyltransferase (also known as Trr). These results provide insight into the molecular mechanisms responsible for the assembly of the zygotic genome at fertilization.

Publication Title

The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization.

Sample Metadata Fields

Specimen part

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accession-icon GSE46988
Expression data from rat spinal cord injury and mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) transplantation
  • organism-icon Rattus norvegicus
  • sample-icon 52 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.1 ST Array (ragene11st)

Description

We analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.

Publication Title

Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

Sample Metadata Fields

Treatment

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accession-icon GSE27092
Expression data from P14 TCR cytotoxic T cells overexpressing HDAC7 phosphorylation deficient mutant
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile.

Publication Title

Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes.

Sample Metadata Fields

Specimen part

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accession-icon GSE33942
Role of PKD2 in TCR-induced transcriptional reprogramming of nave T cells
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Comparison of transcriptional profile of TCR stimulated P14-TCR wild-type and P14-PKD2 null murine lymph node cells

Publication Title

Protein kinase D2 has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE62085
Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex.
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability.

Publication Title

Knockdown of the schizophrenia susceptibility gene <i>TCF4</i> alters gene expression and proliferation of progenitor cells from the developing human neocortex.

Sample Metadata Fields

Sex, Specimen part, Cell line

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accession-icon GSE16674
Analysis of gene expression in miR-34a overexpressing K562 cells
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

miR-34a is strongly induced upon TPA-induced megakaryocyte differentiation of K562 cells. To investigate the gene networks regulated by this miRNA during the process of differentiation we performed gene microarray analysis in K562 cells overexpressing miR-34a or a control sequence.

Publication Title

miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53.

Sample Metadata Fields

Cell line

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accession-icon GSE17859
Microarray analysis of rat hepatic gene expression identifies new genes associated with postprandial triglyceridemia
  • organism-icon Rattus norvegicus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

The acute response four hours after a fat load of extra virgin olive oil was investigated using DNA microarrays. Hepatic gene expression was analysed in Wistar Rats.

Publication Title

Postprandial transcriptome associated with virgin olive oil intake in rat liver.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon SRP050894
mRNA-Seq of the CA1 hippocampal subregion and liver from 3 month and 20 month old animals treated orally with vehicle or SAHA and mRNA-Seq of CA1 of 10 month old WT or APP/PS1-21 transgenic animals treated orally with vehicle or SAHA
  • organism-icon Mus musculus
  • sample-icon 69 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer''s Disease (AD). An effective therapy does not yet exist. Here we use mouse models for age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity at the systems level in the brain and in peripheral organs. We show that at the level of epigenetic gene-expression aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region. While inflammation is associated with increased gene-expression that is linked to a subset of transcription factors, de-regulation of plasticity genes is mediated via different mechanisms in the amyloid and the aging model. Amyloid pathology impairs histone-acetylation and decreases expression of plasticity genes while aging affects differential splicing that is linked to altered H4K12 acetylation at the intron-exon junction in neurons but not in non-neuronal cells. We furthermore show that oral administration of the clinically approved histone deacetylase inhibitor Vorinostat not only restores spatial memory, but also exhibits an anti-inflammatory action and reinstates epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This is the first systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and of the effects of an orally dosed histone deacetylase inhibitor. Our data has important implications for the development of minimally invasive and cost-effective therapeutic strategies against age-associated cognitive decline. In fact, our data strongly suggest to test Vorinostat in patients suffering from AD. Overall design: mRNA profile from aged (CA1 and liver) and APP/PS1 (CA1) animals treated with oral vehicle or SAHA for 4 weeks

Publication Title

HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models.

Sample Metadata Fields

No sample metadata fields

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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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