Surviving Sepsis: bcl-2 Overexpression Modulates Splenocyte Transcriptional Responses in vivo
Transcriptomics Dataset
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General Information
AccessionGSE5811
TitleSurviving Sepsis: bcl-2 Overexpression Modulates Splenocyte Transcriptional Responses in vivo
DescriptionBackground: We hypothesized that spleen microarray gene expression profiles analyzed with contemporary pathway analysis software would provide molecular pathways of interest and target genes that might help explain the affect of bcl-2 on improving survival during sepsis. Methods: Two mouse models of sepsis, cecal ligation and puncture and tracheal instillation of Pseudomonas aeruginosa, were tested in both wild-type mice and mice that overexpress bcl-2. Whole spleens were obtained 6 hours after septic injury. DNA microarray transcriptional profiles were obtained using the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity Pathway Analysis software was used to construct hypothetical transcriptional networks that changed in response to sepsis and expression of the bcl-2 transgene. Results: A conservative approach was used wherein only changes induced by both abdominal and pulmonary sepsis were studied. At 6 hours, sepsis induced alterations in the abundance of hundreds of spleen genes, including a number of proinflammatory mediators (e.g., IL-6). These sepsis-induced alterations were blocked by expression of the bcl-2 transgene. Network analysis implicated a number of bcl-2-related apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and mcl-1. Sepsis in bcl-2 transgenic animals resulted in alteration of RNA abundance for only a single gene, ceacam1. Conclusion: These findings are consistent with sepsis-induced alterations in the balance of pro- and anti-apoptotic transcriptional networks. In addition, our data suggest that the ability of bcl-2 overexpression to improve survival in sepsis in this model is related in part to prevention of sepsis-induced alterations in spleen transcriptional responses. Keywords: Sepsis, bcl-2, wildtype, spleen, RNA expression, microarray
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5811
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

Dataset Accession
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Geneset

Small molecules which mimic BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse BCL2 OE
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in BCL2 OE
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in BCL2 OE
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
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