A global test for groups of genes: testing association with a clinical outcome

Goeman, Jelle J.; Geer, Sara A. van de; Kort, Floor De; Houwelingen, Hans C. van

doi:10.1093/bioinformatics/btg382

Cited by 929 publications

(1,090 citation statements)

References 11 publications

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“…A series of increasingly less stringent filter cutoffs was used to generate several probe set lists of different lengths. These were used as input to the globaltest package in BioConductor (Goeman et al, 2004) to investigate the performance of probe sets when grouped together as a set (rather than treated individually). In this way, a signature comprising the top 50 probe sets was identified (Gene list 3).…”

Section: Microarray Data Analysismentioning

confidence: 99%

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

et al. 2008

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Robust protocols for microarray gene expression profiling of archival formalin-fixed paraffin-embedded tissue (FFPET) are needed to facilitate research when availability of fresh-frozen tissue is limited. Recent reports attest to the feasibility of this approach, but the clinical value of these data is poorly understood. We employed state-of-the-art RNA extraction and Affymetrix microarray technology to examine 34 archival FFPET primary extremity soft tissue sarcomas. Nineteen arrays met stringent QC criteria and were used to model prognostic signatures for metastatic recurrence. Arrays from two paired frozen and FFPET samples were compared: although FFPET sensitivity was low (B50%), high specificity (95%) and positive predictive value (92%) suggest that transcript detection is reliable. Good agreement between arrays and real time (RT) -PCR was confirmed, especially for abundant transcripts, and RT -PCR validated the regulation pattern for 19 of 24 candidate genes (overall R 2 ¼ 0.4662). RT -PCR and immunohistochemistry on independent cases validated prognostic significance for several genes including RECQL4, FRRS1, CFH and MET -whose combined expression carried greater prognostic value than tumour grade -and cmet and TRKB proteins. These molecules warrant further evaluation in larger series. Reliable clinically relevant data can be obtained from archival FFPET, but protocol amendments are needed to improve the sensitivity and broad application of this approach.

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Section: Microarray Data Analysismentioning

confidence: 99%

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

et al. 2008

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“…Using these genes, principal component analysis and unsupervised hierarchical complete linkage clustering was performed to investigate common biological themes present in this data set. The global expression difference of the IBC signature between IBC and non-IBC was investigated using Goeman's global test (Goeman et al, 2004). To investigate if our IBC signature truly reflects the difference between IBC and non-IBC in a platform-independent manner, gene set enrichment analysis (GSEA) was performed (Subramanian et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

et al. 2007

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The present study aims at a platform-independent confirmation of previously obtained cDNA microarray results on inflammatory breast cancer (IBC) using Affymetrix chips. Gene-expression data of 19 IBC and 40 non-IBC specimens were subjected to clustering and principal component analysis. The performance of a previously identified IBC signature was tested using clustering and gene set enrichment analysis. The presence of different cell-of-origin subtypes in IBC was investigated and confirmed using immunohistochemistry on a TMA. Differential gene expression was analysed using SAM and topGO was used to identify the fingerprints of a pro-metastatic-signalling pathway. IBC and non-IBC have distinct gene-expression profiles. The differences in gene expression between IBC and non-IBC are captured within an IBC signature, identified in a platform-independent manner. Part of the gene-expression differences between IBC and non-IBC are attributable to the differential presence of the cell-of-origin subtypes, since IBC primarily segregated into the basal-like or ErbB2-overexpressing group. Strikingly, IBC tumour samples more closely resemble the gene-expression profile of T1/T2 tumours than the gene-expression profile or T3/T4 tumours. We identified the insulin-like growth factor-signalling pathway, potentially contributing to the biology of IBC. Our previous results have been validated in a platform-independent manner. The distinct biological behaviour of IBC is reflected in a distinct gene-expression profile. The fact that IBC tumours are quickly arising tumours might explain the close resemblance of the IBC gene-expression profile to the expression profile of T1/T2 tumours.

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“…A list of D7E-deregulated genes was obtained with a P ϭ 0.05 cutoff. The global test 35 was used to identify significant Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in D7E cells. Clusters with the multiple testing adjusted (Holm's method, P Ͻ 0.05) were selected as significant.…”

Section: Microarray and Transcriptome Analysismentioning

confidence: 99%

Modeling Oculopharyngeal Muscular Dystrophy in Myotube Cultures Reveals Reduced Accumulation of Soluble Mutant PABPN1 Protein

Raz

Routledge

Venema

et al. 2011

The American Journal of Pathology

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Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease caused by an alanine tract expansion mutation in poly(A) binding protein nuclear 1 (expPABPN1). To model OPMD in a myogenic and physiological context, we generated mouse myoblast cell clones stably expressing either human wild type (WT) or expPABPN1 at low levels. Transgene expression is induced on myotube differentiation and results in formation of insoluble nuclear PABPN1 aggregates that are similar to those observed in patients with OPMD. Quantitative analysis of PABPN1 in myotube cultures revealed that expPABPN1 accumulation and aggregation is greater than that of the WT protein. We found that aggregation of expPABPN1 is more affected than WT PABPN1 by inhibition of proteasome activity. Consistent with this, in myotube cultures expressing expPABPN1, deregulation of the proteasome was identified as the most significantly perturbed pathway. Differences in the accumulation of soluble WT and expPABPN1 were consistent with differences in ubiquitination and rate of protein turnover. This study demonstrates, for the first time to our knowledge, that, in myotubes, the ratio of soluble/insoluble expPABPN1 is significantly lower compared with that of the WT protein. We suggest that this difference can contribute to muscle weakness in OPMD.

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A global test for groups of genes: testing association with a clinical outcome

Abstract: An R-package globaltest is available from http://www.bioconductor.org

Cited by 929 publications

References 11 publications

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

Modeling Oculopharyngeal Muscular Dystrophy in Myotube Cultures Reveals Reduced Accumulation of Soluble Mutant PABPN1 Protein

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