Evidence map›Paper›PMID 22558445›Full record

ArticlePloS one2012

Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.

Jing Qin Wu, Xi Wang, Natalie J Beveridge, Paul A Tooney, Rodney J Scott, Vaughan J Carr, Murray J Cairns

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 4% of its field
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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.

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  17. The 14-3-3 Protein Family and Schizophrenia.Frontiers in molecular neuroscience · 2022
    Review
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1 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Jing Qin WuSchizophrenia Research Institute, Sydney, Australia.
Xi Wang
Natalie J Beveridge
Paul A Tooney
Rodney J Scott
Vaughan J Carr
Murray J Cairns
Hunter Medical Research Institute · AUUNSW Sydney · AU

Funding

Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
BRAIN TISSUE RESOURCE CENTER FOR ALCOHOL RESEARCHR24AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI KRIL, JILLIAN JUNE · 2000 to 2011
$2.2M
NIAAA NIH HHS R24 AA012725NIAAA NIH HHS R28 AA012725
6 · The paper itself

Abstract

backgroundWhile hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. METHODOLOGY/PRINCIPAL

findingsThe data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene.

conclusionsThis study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.

Indexed as

Gene Expression ProfilingAdolescentAdultAgedAlternative SplicingBase SequenceCase-Control StudiesCerebral CortexDoublecortin-Like KinasesHumansIntracellular Signaling Peptides and ProteinsMaleMiddle AgedPromoter Regions, GeneticProtein Serine-Threonine KinasesReproducibility of ResultsDCLK1 protein, humanDoublecortin-Like KinasesIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesRNA IsoformsRNA, Messenger

Identifiers

PMID22558445
PMCPMC3338678
OpenAlexW2089358134

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LicenceCC BY
Read underepoch 390

Registered trials

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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.