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accession-icon GSE117463
Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Human mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.

Publication Title

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.

Sample Metadata Fields

Treatment

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accession-icon SRP187597
Intrinsic Resistance to MEK Inhibition Through BET Protein Mediated Kinome
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.

Publication Title

Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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accession-icon E-MEXP-1480
Transcription profiling by array of Arabidopsis plants after innoculation with isogenic Pseudomonas syringaie strains expressing one of four different avr genes
  • organism-icon Arabidopsis thaliana
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis Genome Array (ag)

Description

Gene expression profiles of a single Arabidopsis genotype (Col-0) in response to isogenic Pseudomonas syringae strains expressing one of four different cloned avr genes was studied (avrRpt2, avrRpm1, avrPphB, avrRps4; responses mediated by the R genes RPS2, RPM1, RPS5 and RPS4 ).

Publication Title

Discovery of ADP-ribosylation and other plant defense pathway elements through expression profiling of four different Arabidopsis-Pseudomonas R-avr interactions.

Sample Metadata Fields

Age, Specimen part, Disease, Disease stage

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accession-icon GSE27345
Expression data from Drosophila melanogaster adults which contain transgenes to deliver a knockdown effect of Dhr96 expression, or over-expression of Dhr96, compared to control flies.
  • organism-icon Drosophila melanogaster
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2), Affymetrix Drosophila Genome Array (drosgenome1)

Description

To investigate the systemic molecular changes occurring as a result of Dhr96 knockdown or over-expression, a comparison between knockdown or overexpression lines and their genetic controls were performed. 0-3 day old adult males or females were reared on 3 separate batches of diet (this was the standard diet we used for culturing Drosophila melanogaster and was made up of 10L water, 100g agar (USP #7060 Bio-serve), 350g Brewers dried yeast (Sunshine Health), 300g black treacle (Lyles), 150g sucrose (Tate & Lyle), 300g Difco dextrose (Becton Dickinson), 150g cornmeal (#1151, Bioserve), 100g wheatgerm (#1659, Bioserve), 200g soya bean flour (#S9633 Sigma Aldrich), 10g methyl-4-hydroxybenzoate (#H3647 Sigma Aldrich) in 10ml ethanol, 50ml proprionic acid (#P5561 Sigma Aldrich)). Each of these 3 batches was considered to represent independent biological replication. The RNA samples were hybridized to the Affymetrix Drosophila GeneChip 2.

Publication Title

Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE27376
Effects of altered levels of Cyp6g1 and of Dhr96 on gene expression in Drosophila
  • organism-icon Drosophila melanogaster
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE27344
Expression data from transgenic Drosophila melanogaster adults which contain a knockdown effector of cyp6g1, compared to control flies
  • organism-icon Drosophila melanogaster
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome Array (drosgenome1)

Description

To test whether other genes were being silenced in the Cyp6g1 knockdown strain due to off-target RNAi effects, and whether other gene expression changes were contributing to the altered susceptibility to imidacloprid in these knockdown flies. A comparison between w;Act5C-GAL4/CyO; UAS:RNAi_Cyp6g1Hp2/TM3Sb and the genetic control w;Act-GAL4/CyO;+/TM3Sb was performed. Ten 2-3 day old adult males or females were transferred to sugar-agar plates and then collected at various time points (0, 2, 5, 8 hours). The RNA samples for up to three independent experiments per timepoint for each genotype were then pooled, in equal concentrations, before hybridisation to the Affymetrix Drosophila GeneChip 1.

Publication Title

Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.

Sample Metadata Fields

Sex, Specimen part, Time

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accession-icon GSE7138
Induction of Dendritic Cell-like Phenotype in Macrophages during Foam Cell Formation
  • organism-icon Homo sapiens
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

Foam cell formation from monocyte-derived macrophages is a hallmark of atheroscle-rotic lesions. Aspects of this process can be recapitulated in vitro by exposing MCSF-induced or platelet factor4 (CXCL4)-induced macrophages to oxidized (ox) or minimally modified (mm) low density lipoprotein (LDL). We measured gene expression in periph-eral blood mononuclear cells (PBMCs), monocytes and macrophages treated with CXCL1 (GRO-) or CCL2 (MCP-1) as well as foam cells induced by native LDL, mmLDL or oxLDL using 22 Affymetrix gene chips. Using an advanced Bayesian error-pooling approach and a heterogeneous error model (HEM) with a false discovery rate (FDR) <0.05, we found 5,303 of 22,215 probe sets to be significantly regulated in at least one of the conditions. Among a subset of 917 candidate genes that were preselected for their known biological functions in macrophage foamcell differentiation, we found that 290 genes met the above statistical criteria for significant differential expression patterns. While many expected genes were found to be upregulated by LDL and oxLDL, very few were induced by mmLDL. We also found induction of unexpected genes, most strikingly MHC-II and other dendritic cell markers such as CD11c. The gene expression patterns in response to oxLDL were similar in MCSF-induced and CXCL4-induced macrophages. Our findings suggest that LDL and oxLDL, but not mmLDL, induce a dendritic cell-like phenotype in macrophages, suggesting that these cells may be able to present antigens and support an immune response.

Publication Title

Induction of dendritic cell-like phenotype in macrophages during foam cell formation.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP033104
Lsh regulates LTR retrotransposon repression independent of Dnmt3b function (RNA-Seq)
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1000

Description

Background: Global DNA methylation contributes to genomic integrity by supressing repeat associated transposition events. Several chromatin factors are required in addition to DNA methyltransferases to maintain DNA methylation at intergenic and satellite repeats. Embryos lacking Lsh, a member of the SNF2 superfamily of chromatin helicases, are hypomethylated. The interaction of Lsh with the de novo methyltransferase, Dnmt3b, facilitates the deposition of DNA methylation at stem cell genes. We wished to determine if a similar targeting mechanism operates to maintain DNA methylation at repetitive sequences. Results: We used HELP-seq to map genome wide DNA methylation patterns in Lsh-/- and Dnmt3b-/- somatic cells. DNA methylation is predominantly lost from specific genomic repeats in Lsh-/- cells: LTR-retrotransposons, LINE-1 repeats and mouse satellites. RNA-seq experiments demonstrate that specific IAP (Intracisternal A-type particle) LTRs and satellites, but not LINE-1 elements, are aberrantly transcribed inLsh-/- cells. LTR hypomethylation in Dnmt3b-/- cells is moderate and hypomethylated repetitive elements (IAP, LINE-1 and satellite) are silent. Chromatin immunoprecipitation (ChIP) indicates that repressed LINE-1 elements gain H3K4me3, but H3K9me3 levels are unaltered in Lsh-/- cells, indicating that DNA hypomethylation alone is not permissive for their transcriptional activation. Mis-expressed IAPs and satellites lose H3K9me3 and gain H3K4me3 in Lsh-/- cells. Conclusions: Our study emphasizes that regulation of repetitive elements by DNA methylation is selective and context dependent. We propose a model where Lsh is specifically required at a precise developmental window to target de novo methylation to repeat sequences, which is subsequently maintained by Dnmt1 in somatic cells to enforce repeat silencing thus contributing to genomic integrity. Overall design: Two pairs of RNA samples compared: WT and Lsh-/- RNA isolations from tail-tip fibroblasts; WT and Lsh-/- RNA isolations from E13.5 mouse embryos.

Publication Title

Lsh regulates LTR retrotransposon repression independently of Dnmt3b function.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP098927
A Cross-Species Approach Identifies MELK as a Potential Therapeutic Target in Prostate Cancer
  • organism-icon Mus musculus
  • sample-icon 912 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Genetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples

Publication Title

Identification of potential therapeutic targets in prostate cancer through a cross-species approach.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE9460
Mouse model of Osteosarcoma
  • organism-icon Mus musculus
  • sample-icon 26 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

expression analysis from a genetically engineered mouse model of osteosarcoma

Publication Title

Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease.

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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