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dc.contributor.author Robinson, TJ
dc.contributor.author Dinan, MA
dc.contributor.author Dewhirst, M
dc.contributor.author Garcia-Blanco, MA
dc.contributor.author Pearson, JL
dc.coverage.spatial England
dc.date.accessioned 2011-06-21T17:27:56Z
dc.date.issued 2010-02-25
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20184770
dc.identifier 1471-2105-11-108
dc.identifier.citation BMC Bioinformatics, 2010, 11 pp. 108 - ?
dc.identifier.uri http://hdl.handle.net/10161/4332
dc.description.abstract BACKGROUND: Over the past two decades more than fifty thousand unique clinical and biological samples have been assayed using the Affymetrix HG-U133 and HG-U95 GeneChip microarray platforms. This substantial repository has been used extensively to characterize changes in gene expression between biological samples, but has not been previously mined en masse for changes in mRNA processing. We explored the possibility of using HG-U133 microarray data to identify changes in alternative mRNA processing in several available archival datasets. RESULTS: Data from these and other gene expression microarrays can now be mined for changes in transcript isoform abundance using a program described here, SplicerAV. Using in vivo and in vitro breast cancer microarray datasets, SplicerAV was able to perform both gene and isoform specific expression profiling within the same microarray dataset. Our reanalysis of Affymetrix U133 plus 2.0 data generated by in vitro over-expression of HRAS, E2F3, beta-catenin (CTNNB1), SRC, and MYC identified several hundred oncogene-induced mRNA isoform changes, one of which recognized a previously unknown mechanism of EGFR family activation. Using clinical data, SplicerAV predicted 241 isoform changes between low and high grade breast tumors; with changes enriched among genes coding for guanyl-nucleotide exchange factors, metalloprotease inhibitors, and mRNA processing factors. Isoform changes in 15 genes were associated with aggressive cancer across the three breast cancer datasets. CONCLUSIONS: Using SplicerAV, we identified several hundred previously uncharacterized isoform changes induced by in vitro oncogene over-expression and revealed a previously unknown mechanism of EGFR activation in human mammary epithelial cells. We analyzed Affymetrix GeneChip data from over 400 human breast tumors in three independent studies, making this the largest clinical dataset analyzed for en masse changes in alternative mRNA processing. The capacity to detect RNA isoform changes in archival microarray data using SplicerAV allowed us to carry out the first analysis of isoform specific mRNA changes directly associated with cancer survival.
dc.format.extent 108 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof BMC Bioinformatics
dc.relation.isversionof 10.1186/1471-2105-11-108
dc.subject Algorithms
dc.subject Biomarkers, Tumor
dc.subject Data Mining
dc.subject Databases, Genetic
dc.subject Gene Expression Profiling
dc.subject Neoplasms
dc.subject Oligonucleotide Array Sequence Analysis
dc.subject Protein Isoforms
dc.subject RNA, Messenger
dc.subject Software
dc.title SplicerAV: a tool for mining microarray expression data for changes in RNA processing.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-2-25 en_US
duke.description.endpage 108 en_US
duke.description.issue en_US
duke.description.startpage 108 en_US
duke.description.volume 11 en_US
dc.relation.journal Bmc Bioinformatics en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20184770
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Biomedical Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Medical Oncology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Radiation Oncology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Clinical Research Institute
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1471-2105

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