Sanjana Sood
iGEMS: an integrated model for identification of alternative exon usage events
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.
Authors
Krzysztof J. Szkop
Asif Nakhuda
Iain J. Gallagher
Carl Murie
Robert J. Brogan
Jaakko Kaprio
Heikki Kainulainen
PHILIP ATHERTON philip.atherton@nottingham.ac.uk
Professor of Clinical, metabolic & Molecular Physiology
Urho M. Kujala
Thomas Gustafsson
Ola Larsson
James A. Timmons
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.
Citation
Sood, S., Szkop, K. J., Nakhuda, A., Gallagher, I. J., Murie, C., Brogan, R. J., …Timmons, J. A. (2016). iGEMS: an integrated model for identification of alternative exon usage events. Nucleic Acids Research, 44(11), e109. https://doi.org/10.1093/nar/gkw263
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 2, 2016 |
Online Publication Date | Apr 19, 2016 |
Publication Date | Jun 20, 2016 |
Deposit Date | Sep 6, 2018 |
Publicly Available Date | May 6, 2020 |
Journal | Nucleic Acids Research |
Print ISSN | 0305-1048 |
Electronic ISSN | 1362-4962 |
Publisher | Oxford University Press |
Peer Reviewed | Peer Reviewed |
Volume | 44 |
Issue | 11 |
Pages | e109 |
DOI | https://doi.org/10.1093/nar/gkw263 |
Public URL | https://nottingham-repository.worktribe.com/output/1117694 |
Publisher URL | https://academic.oup.com/nar/article/44/11/e109/2468305 |
PMID | 27095197 |
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iGEMS: an integrated model for identification of alternative exon usage events
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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