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Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: iGEMS: an integrated model for identification of alternative exon usage events
Authors: Sood, Sanjana
Szkop, Krzysztof J
Nakhuda, Asif
Gallagher, Iain J
Murie, Carl
Brogan, Robert J
Kaprio, Jaakko
Kainulainen, Heikki
Atherton, Philip J
Kujala, Urho M
Gustafsson, Thomas
Larsson, Ola
Timmons, James A
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Issue Date: 20-Jun-2016
Publisher: Oxford University Press
Citation: Sood S, Szkop KJ, Nakhuda A, Gallagher IJ, Murie C, Brogan RJ, Kaprio J, Kainulainen H, Atherton PJ, Kujala UM, Gustafsson T, Larsson O & Timmons JA (2016) iGEMS: an integrated model for identification of alternative exon usage events, Nucleic Acids Research, 44 (11), Art. No.: e109.
Abstract: DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (∼90\%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95\%, n = 22). Importantly, iGEMS identified a variety of AEU events, including 3′UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identification of AEU while the variety of exon usage between human tissues is 5–10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.
Type: Journal Article
DOI Link:
Rights: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Affiliation: King's College London
King's College London
King's College London
Karolinska Institutet
XRGenomics Ltd
University of Helsinki
University of Jyvaskyla, Finland
University of Nottingham
University of Jyvaskyla, Finland
Karolinska University Hospital
Karolinska Institutet
King's College London

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