ArticleBMC bioinformatics2010
SplicerAV: a tool for mining microarray expression data for changes in RNA processing.
Article in BMC bioinformatics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Enhanced information output from shotgun proteomics data by protein quantification and peptide quality control (PQPQ).Molecular & cellular proteomics : MCP · 2011Pooled it
- Inhibition of Epidermal Growth Factor Receptor Signaling by Antisense Oligonucleotides as a Novel Approach to Epidermal Growth Factor Receptor Inhibition.Nucleic acid therapeutics · 2022Article
- Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Unique Transcriptional Programs Identify Subtypes of AKI.Journal of the American Society of Nephrology : JASN · 2017Article
- Sources of high variance between probe signals in Affymetrix short oligonucleotide microarrays.Sensors (Basel, Switzerland) · 2013Article
- Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are important for the maintenance of latency.Journal of virology · 2013Article
- Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks.BMC research notes · 2013Article
- SplicerEX: a tool for the automated detection and classification of mRNA changes from conventional and splice-sensitive microarray expression data.RNA (New York, N.Y.) · 2012Article
- Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.RNA (New York, N.Y.) · 2011Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOver 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.
resultsData 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.
conclusionsUsing 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.