Evidence map›Paper›PMID 30504444›Full record

ArticleAnnals of the rheumatic diseases2019

RNA sequencing data integration reveals an miRNA interactome of osteoarthritis cartilage.

Rodrigo Coutinho de Almeida, Yolande F M Ramos, Ahmed Mahfouz, Wouter den Hollander, Nico Lakenberg, Evelyn Houtman, Marcella van Hoolwerff, H Eka D Suchiman, Alejandro Rodríguez Ruiz, P Eline Slagboom and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 1% 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

102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.

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42 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

15 authors at 1 institution in 1 country.

Rodrigo Coutinho de Almeida *Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Yolande F M Ramos *Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ahmed MahfouzThe Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
Wouter den HollanderDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Nico LakenbergDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Evelyn HoutmanDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Marcella van HoolwerffDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
H Eka D SuchimanDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-7168-5516
Alejandro Rodríguez RuizDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
P Eline SlagboomDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Hailiang MeiSequence Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands.
Szymon M KiełbasaDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Rob G H H NelissenDepartment of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
Marcel ReindersDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ingrid MeulenbeltDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands i.meulenbelt@lumc.nl.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.

methodsWe performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed differential expression (DE) analysis of miRNA and mRNAs. To build an OA-specific miRNA interactome, a prioritisation scheme was applied based on inverse Pearson's correlations and inverse DE of miRNAs and mRNAs. Subsequently, these were filtered by those present in predicted (TargetScan/microT-CDS) and/or experimentally validated (miRTarBase/TarBase) public databases. Pathway enrichment analysis was applied to elucidate OA-related pathways likely mediated by miRNA regulatory mechanisms.

resultsWe found 142 miRNAs and 2387 mRNAs to be differentially expressed between lesioned and preserved OA articular cartilage. After applying prioritisation towards likely miRNA-mRNA targets, a regulatory network of 62 miRNAs targeting 238 mRNAs was created. Subsequent pathway enrichment analysis of these mRNAs (or genes) elucidated that genes within the 'nervous system development' are likely mediated by miRNA regulatory mechanisms (familywise error=8.4×10

conclusionsBy an integrated approach of miRNA and mRNA sequencing data of OA cartilage, an OA miRNA interactome and related pathways were elucidated. Our functional data demonstrated interacting levels at which miRNA affects expression of genes in the cartilage and exemplified the complexity of functionally validating a network of genes that may be targeted by multiple miRNAs.

Indexed as

Cartilage, ArticularComputational BiologyHumansMicroRNAsOsteoarthritisRNA, MessengerSequence Analysis, RNAMicroRNAsRNA, Messengerdata integrationmicroRNAsmRNAosteoarthritisregulatory networks

Identifiers

PMID30504444
PMCPMC6352405
OpenAlexW2908918388

What OpenQuestion holds

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LicenceCC BY-NC
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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.