Evidence map›Paper›PMID 27095197›Full record

ArticleNucleic acids research2016

iGEMS: an integrated model for identification of alternative exon usage events.

Sanjana Sood, Krzysztof J Szkop, Asif Nakhuda, Iain J Gallagher, Carl Murie, Robert J Brogan, Jaakko Kaprio, Heikki Kainulainen, Philip J Atherton, Urho M Kujala and 3 more

Abstract readTwin Study
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Trial
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  4. Review
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  6. Article
  7. Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Sanjana SoodDivision of Genetics and Molecular Medicine, King's College London, WC2R 2LS, London, UK Research Department, XRGenomics Ltd, 35 Kingsland Road, London E2 8AA, UK.
Krzysztof J SzkopDivision of Genetics and Molecular Medicine, King's College London, WC2R 2LS, London, UK Research Department, XRGenomics Ltd, 35 Kingsland Road, London E2 8AA, UK.
Asif NakhudaDivision of Genetics and Molecular Medicine, King's College London, WC2R 2LS, London, UK School of Medicine, University of Nottingham, Derby Royal Hospital, Derbyshire, DE22 3DT, UK.
Iain J GallagherSchool of Health Sciences, University of Stirling, Stirling, FK9 4LA, Scotland.
Carl MurieDepartment of Oncology-Pathology, SciLifeLab, Karolinska Institutet, 171 76 Stockholm, Sweden.
Robert J BroganResearch Department, XRGenomics Ltd, 35 Kingsland Road, London E2 8AA, UK.
Jaakko KaprioDepartment of Public Health and the Institute for Molecular Medicine (FIMM), University of Helsinki, FI-00014, Helsinki, Finland National Institute for Health and Welfare, University of Helsinki, FI-00014, Helsinki, Finland.
Heikki KainulainenDepartment of Biology of Physical Activity, University of Jyväskylä, FI-40014, Jyväskylä, Finland.
Philip J AthertonSchool of Medicine, University of Nottingham, Derby Royal Hospital, Derbyshire, DE22 3DT, UK.
Urho M KujalaDepartment of Health Sciences, University of Jyväskylä, FI-40014, Jyväskylä, Finland.
Thomas GustafssonDepartment of Laboratory Medicine, Division of Clinical Physiology, Karolinska University Hospital, 14186, Huddinge, Sweden.
Ola LarssonDepartment of Oncology-Pathology, SciLifeLab, Karolinska Institutet, 171 76 Stockholm, Sweden.
James A TimmonsDivision of Genetics and Molecular Medicine, King's College London, WC2R 2LS, London, UK Research Department, XRGenomics Ltd, 35 Kingsland Road, London E2 8AA, UK Jamie.Timmons@gmail.com.

Funding

Biotechnology and Biological Sciences Research Council BB/G013128/1Medical Research Council G1100015
6 · The paper itself

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.

Indexed as

Alternative SplicingExonsAdultAnimalsComputational BiologyGene Expression ProfilingGenomicsHumansMiceOligonucleotide Array Sequence AnalysisTranscriptome

Identifiers

PMID27095197
PMCPMC4914109

What OpenQuestion holds

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Registered trials

None linked

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.