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Homo sapiens
4 Downloadable Samples
Illumina 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
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
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
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- 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
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
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
View Samples- Drosophila melanogaster
- 14 Downloadable Samples
- 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
View Samples- Homo sapiens
- 22 Downloadable Samples
- 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
View Samples- Mus musculus
- 912 Downloadable Samples
- Illumina 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
View Samples
GSE9460- Mus musculus
- 26 Downloadable Samples
- 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
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of gene expression by RNA-seq upon siRNA mediated knockdown of scaffold attachment factor A (SAF-A) versus control siRNA in RPE1 cells at 24 hour and 48 hour time points post transfection reveals SAF-A loss does not impact on gene transcription Overall design: Two control RNA-seq libraries where produced (24h and 48h) to compare to the two SAF-A siRNA knockdown RNA-seq libraries, each was a single experimental replicate.
Publication Title
SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Small molecule BET bromodomain inhibitors (BETi) are actively being pursued in clinical trials for the treatment of a variety of cancers, however, the mechanisms of resistance to targeted BET protein inhibitors remain poorly understood. Using a novel mass spectrometry approach that globally measures kinase signaling at the proteomic level, we evaluated the response of the kinome to targeted BET inhibitor treatment in a panel of BRD4-dependent ovarian carcinoma (OC) cell lines. Despite initial inhibitory effects of BETi, OC cells acquired resistance following sustained treatment with the BETi, JQ1. Through application of Multiplexed Inhibitor Beads (MIBs) and mass spectrometry, we demonstrate that BETi resistance is mediated by adaptive kinome reprogramming, where activation of compensatory pro-survival kinase networks overcomes BET protein inhibition. Furthermore, drug combinations blocking these kinases may prevent or delay the development of drug resistance and enhance the efficacy of BET inhibitor therapy. Overall design: RNAseq was employed to identify changes in kinase RNA expression following short term (48h) or chronic (JQ1R) JQ1 treatment in three different ovarian cancer cell lines.
Publication Title
Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer.
Sample Metadata Fields
Cell line, Subject
View Samples