Comparison of the genetic extinction of NRAS to pharmacological MEK inhibition in an inducible mouse model of melanoma
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
AccessionGSE39984
TitleComparison of the genetic extinction of NRAS to pharmacological MEK inhibition in an inducible mouse model of melanoma
DescriptionSince direct pharmacological inhibition of RAS has thus far been unsuccessful, we explored system biology approaches to identify synergistic drug combination(s) that can mimic direct RAS inhibition. Leveraging an inducible mouse model of NRAS-mutant melanoma, we compare pharmacological MEK inhibition to complete NRAS-Q61K extinction in vivo. NRAS-Q61K extinction leads to a complete and durable tumor regression by enhancing both apoptosis and cell cycle arrest. By contrast, MEK inhibition only produces tumor stasis at best and we find that it robustly activates apoptosis but does not significantly impede proliferation. We used microarrays to determine which transcripts were affected by NRAS-Q61K extinction but insufficiently by MEK inhibition. We selected a single comparative timepoint, 4 days post-treatment. Downstream analyses included GSEA and TRAP algorithms, leading to the identification of a differentially affected CDK4-driven proliferation network. Immune genes were also identified as significant, but control experiments determined these to be largely the off-target effects of doxycycline and not of NRAS-Q61K extinction.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39984
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic MAP2K1 druginhibition
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MAP2K1 druginhibition
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in MAP2K1 druginhibition
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in MAP2K1 druginhibition
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in MAP2K1 druginhibition
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in MAP2K1 druginhibition
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in MAP2K1 druginhibition
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.