Analysis of Gene Expression Data Using BRB-Array Tools

Simon, Richard; Lam, Amy; Li, Ming-Chung; Ngan, Michael; Menenzes, Supriya; Zhao, Yingdong

doi:10.1177/117693510700300022

Cited by 614 publications

(599 citation statements)

References 30 publications

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“…Statistical tests were performed using BRB-ArrayTools developed by Richard Simon and the BRB-ArrayTools Development Team (21). A Student t test was used to identify genes significantly different in the following comparisons: Cav-1 KO Dex versus vehicle, C57 Dex versus vehicle, and Cav-1 KO versus C57 vehicle.…”

Section: Methodsmentioning

confidence: 99%

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

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While glucocorticoids (GCs) are used clinically to treat many conditions, their neonatal and prenatal usage is increasingly controversial due to reports of delayed adverse outcomes, especially their effects on brain development. Such alterations may reflect the impact of GCs on neural progenitor/stem cell (NPSC) function. We previously demonstrated that the lipid raft protein caveolin-1 (Cav-1) was required for rapid GC signaling in embryonic mouse NPSCs operating through plasma membranebound glucocorticoid receptors (GRs). We show here that genomic GR signaling in NPSCs requires Cav-1. Loss of Cav-1 impacts the transcriptional response of many GR target genes (e.g., the serum-and glucocorticoid-regulated kinase 1 gene) that are likely to mediate the antiproliferative effects of GCs. Microarray analysis of wild-type C57 or Cav-1-deficient NPSCs identified approximately 100 genes that are differentially regulated by GC treatment. These changes in hormone responsiveness in Cav-1 knockout NPSCs are associated with the loss of GC-regulated phosphorylation of GR at serine 211 but not at serine 226. Chromatin recruitment of total GR to regulatory regions of target genes such as Fkbp-5, RhoJ, and Sgk-1, as well as p211-GR recruitment to Sgk-1, are compromised in Cav-1 knockout NPSCs. Cav-1 is therefore a multifunctional regulator of GR in NPSCs influencing both rapid and genomic action of the receptor to impact cell proliferation.

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Section: Methodsmentioning

confidence: 99%

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

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“…21 Statistical analyses were performed using MedCalc (MedCalc Inc., Mariakerke, Belgium). An online gene expression analysis system (ChipDX) was developed with R, Bioconductor, Microsoft ASP.net, and SQL Server (Microsoft Corporation, Redmond, WA).…”

Section: Resultsmentioning

confidence: 99%

“…A modified version of the method described by Bair and Tibshirani, 18 implemented in a package (BRB ArrayTools), 19 was used to develop and train a predictive algorithm to stratify patients into categories corresponding to a high or low risk of disease recurrence. This method uses Cox proportional hazards (CPH) models to relate RFS to a specified number of "metagene" expression levels (ie, principal component linear combinations of expression data).…”

Section: Prognostic Gene Selection and Algorithm Trainingmentioning

confidence: 99%

Design and Multiseries Validation of a Web-Based Gene Expression Assay for Predicting Breast Cancer Recurrence and Patient Survival

Laar¹

2011

The Journal of Molecular Diagnostics

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Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a "metagene" algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use.

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“…The arrays were analysed using the BRB data analysis tools for Excel (Simon et al 2007) and normalized using the median. These data were then used to identify the genes with differential expression using the MeV4.0 software package (Saeed et al 2006).…”

Section: Microarray Analysismentioning

confidence: 99%

Genes commonly involved in acid tolerance are not overexpressed in the plant microsymbiont Mesorhizobium loti MAFF303099 upon acidic shock

Laranjo

Alexandre

Oliveira

2014

Appl Microbiol Biotechnol

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Rhizobia are legume bacterial symbionts that fix nitrogen in the root nodules of plants. The aim of the present study was to investigate the global transcriptional response of rhizobia upon an acidic shock. Changes in the transcriptome of cells of Mesorhizobium loti strain MAFF303099 upon an acidic shock at pH 3 for 30 min were analysed. From a total of 7,231 protein-coding genes, 433 were found to be differentially expressed upon acidic shock, of which 322 were overexpressed. Although most of the overexpressed genes encode hypothetical proteins, the two most represented Cluster of Orthologous Group (COG) categories are 'defence mechanisms' and 'transcription'. Differentially expressed genes are dispersed throughout the chromosome, with the exception of the symbiosis island, where most genes remain unchanged. A significant number of transcriptional regulators and ABC transporter genes are overexpressed. No overexpression of genes typically associated to acid tolerance in rhizobia, such as act and exo genes, was detected. Overall, this study suggests a transcriptional response to acidic shock of M. loti distinct from other rhizobia. Additional studies are in course to explore the role of some of the highly overexpressed genes and to further elucidate the molecular bases of acid stress response.

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Analysis of Gene Expression Data Using BRB-Array Tools

Cited by 614 publications

References 30 publications

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Design and Multiseries Validation of a Web-Based Gene Expression Assay for Predicting Breast Cancer Recurrence and Patient Survival

Genes commonly involved in acid tolerance are not overexpressed in the plant microsymbiont Mesorhizobium loti MAFF303099 upon acidic shock

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