SplicerAV: a tool for mining microarray expression data for changes in RNA processing.
Timothy J. Robinson,Michaela A. Dinan,Mark W. Dewhirst,Mariano A. Garcia-Blanco,James L. Pearson +4 more
TL;DR: The capacity to detect RNA isoform changes in archival microarray data using SplicerAV allowed the first analysis of isoform specific mRNA changes directly associated with cancer survival, and revealed a previously unknown mechanism of EGFR activation in human mammary epithelial cells.
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Abstract: 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. 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. 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.
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•Journal Article
Discovery of Novel Splice Forms and Functional Analysis of Cancer-Specific Alternative Splicing in Human Expressed Sequences
TL;DR: A genome-wide analysis of alternative splicing in 2 million human expressed sequence tags (ESTs), to identify splice forms that are up-regulated in tumors relative to normal tissues suggests that many of these shifts act by disrupting a tumor suppressor function.
183
Unique Transcriptional Programs Identify Subtypes of AKI
Katherine Xu,Paul E. Rosenstiel,Neal Paragas,Christian Hinze,Xiaobo Gao,Tian Huai Shen,Max Werth,Catherine S. Forster,Rong Deng,Efrat Bruck,Roger W. Boles,Alexandra Tornato,Tejashree S. Gopal,Madison Jones,Justin Konig,Jacob Stauber,Vivette D. D'Agati,Hediye Erdjument-Bromage,Subodh J. Saggi,Gebhard Wagener,Kai M. Schmidt-Ott,Nicholas P. Tatonetti,Paul Tempst,Juan A. Oliver,Paolo Guarnieri,Jonathan Barasch +25 more
TL;DR: iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify the current definitions of acute changes in kidney excretory function.
123
Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities
Timothy J. Robinson,Jennifer A. Freedman,Muthana Al Abo,April Deveaux,Bonnie LaCroix,Brendon M. Patierno,Daniel J. George,Steven R. Patierno +7 more
TL;DR: This perspective aims to increase awareness of alternative RNA splicing, propose immediate opportunities to improve identification and analysis of ARS, and call for bioinformaticians and cancer researchers to work together to address the urgent need to incorporate ARS into cancer biology and precision oncology.
Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing
Heather B. Miller,Timothy J. Robinson,Raluca Gordân,Raluca Gordân,Alexander J. Hartemink,Mariano A. Garcia-Blanco +5 more
TL;DR: Findings suggest that Tat-SF1 functions independently in transcription and splicing of cellular genes.
Sexual dimorphism of miRNA signatures in feto-placental endothelial cells is associated with altered barrier function and actin organization
Silvija Cvitic,Jasmin Strutz,Hannah M Appel,Elisa Weiß,Waltraud Brandl,Andrea Thüringer,Eva Bernhart,Luciana Lassance,Christian Wadsack,Carolin Schliefsteiner,Ivana Sreckovic,Karl Kashofer,Ursula Hiden +12 more
TL;DR: Three distinct miRNA expression patterns in male vs female human endothelial cells which contribute to the functional differences are hypothesized and potentially affected biological functions are analyzed.
16
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