Evidence map›Paper›PMID 36266270›Full record

ArticleNature communications2022

Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function.

Richard I Ainsworth, Deepa Hammaker, Gyrid Nygaard, Cecilia Ansalone, Camilla Machado, Kai Zhang, Lina Zheng, Lucy Carrillo, Andre Wildberg, Amanda Kuhs and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.7field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 37 citations in OpenAlex.

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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

14 authors at 2 institutions in 3 countries.

Richard I AinsworthDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Deepa HammakerDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Gyrid NygaardDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Cecilia AnsaloneDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Camilla MachadoDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0001-6584-195X
Kai ZhangDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Lina ZhengBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-3992-3289
Lucy CarrilloDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Andre WildbergDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Amanda KuhsDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Mattias N D SvenssonDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
David L BoyleDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Gary S FiresteinDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA. gfirestein@health.ucsd.edu.ORCID 0000-0003-3495-960X
Wei WangDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA. wei-wang@ucsd.edu.ORCID 0000-0003-4377-5060
University of California San Diego · USHaukeland University Hospital · NO

Funding

Identification of key regulators in rheumatoid arthritisR01AR065466 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, WANG, WEI · 2014 to 2024
$4.6M
Resource-based Center for the study of the joint microenvironment in rheumatology (Overall Application)P30AR073761 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CORR, MARY P · 2018 to 2022
$3.9M
Joint-location specific pathogenic pathways in rheumatoid arthritisR01AR071321 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, WANG, WEI · 2018 to 2023
$1.7M
NIAMS NIH HHS P30 AR073761NIAMS NIH HHS R01 AR065466NIAMS NIH HHS R01 AR071321
6 · The paper itself

Abstract

Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted active pathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.

Indexed as

Arthritis, RheumatoidSynoviocytesCell LineCell ProliferationCells, CulturedFibroblastsHumansSynovial MembraneSystems BiologyTranscription FactorsTransfer FactorTransforming Growth Factor betaTranscription FactorsTransfer FactorTransforming Growth Factor beta

Identifiers

PMID36266270
PMCPMC9584907
OpenAlexW4306880074

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.