GSE195557

TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation

Whole-study status Not suitable

Dataset does not meet the current suitability threshold.

Whole-study downloads — these do not apply your sample requirements.

Selected cohort requirements

Samples meeting selected requirements: 0 cases / 0 controls

View matching samples

8 case / 8 control samples elsewhere in the study have incomplete or conflicting evidence; they are not included above

Patient pairs verified in indexed sample metadata: 0

A case/control comparison meeting these requirements is not confirmed.

Counts describe samples, not independent patients. Pair verification uses explicit subject identifiers in indexed sample metadata. Zero verified pairs does not establish that the study is unpaired; reported matched-normal design alone is insufficient.

Source: GEO
Assay: bulk RNA-seq
Organism: Homo sapiens
Whole-study samples: 16 samples
Specimen: Tissue
Reported/interpreted study design: Treatment vs control Design classification does not establish patient pairs.

Comparison type: Tumor vs normal
Contributors: Tosevska A, Karonitsch T
Contact name: Anela Tosevska
Submission date: 2022-01-27
Last update: 2022-08-05
Organization: Medical Univrsity of Vienna
Department: Division of Rheumatology
Public date: 2022-04-26
Experiment types: Expression profiling by high throughput sequencing
Platforms: GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Series type: Series
SubSeries: Not available
BioProject: PRJNA801247

Summary

Objectives: TNF-induced activation of fibroblast-like synoviocytes (FLS) is a critical determinant for synovial inflammation and joint destruction in rheumatoid arthritis (RA). The detrimental role of TNF-receptor 1 (TNFR1) has thoroughly been characterized. The contributions of TNFR2, however, are largely unknown. This study was performed to delineate the role of TNFR2 in human FLS activation. Methods: TNFR2 expression in synovial tissue samples was determined by immunohistochemistry. Expression of TNFR2 was silenced using RNAi or CRISPR/Cas9 technologies. Global transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to validate RNA-seq results and to uncover pathways operating downstream of TNFR2 in FLS. Results. TNFR2 expression was increased in RA when compared to OA synovial tissues. In particular, RA-FLS demonstrated higher levels of TNFR2 when compared to OA-FLS. TNFR2 expression in RA-FLS correlated with RA disease activity, synovial T- and B-cell infiltration. TNF and IL1 were identified as inflammatory mediators that upregulate TNFR2 in RA-FLS. Silencing of TNFR2 in RA-FLS markedly diminished the TNF-induced expression of inflammatory cytokines and chemokines, including CXCR3-binding chemokines and the B-cell activating factor TNFSF13B. Immunobiochemical analyses revealed that TNFR2-mediated expression of inflammatory mediators critically depends on STAT1. Conclusion: Our results define a critical role for TNFR2 in FLS-driven inflammation and unfold its participation in the unresolved course of synovial inflammation in RA.

Overall design

Examining the effect of TNFR2 knockdown on gene expression in TNF-stimulated fibroblast-like synoviocytes (FLS)

Source Evidence

4 sources

Source	Contribution	Status
GEO	Original dataset metadata, sample metadata, source links, and GEO data availability flags. Sample records 16 GSM samples	Primary source
recount3	Planned trusted source for processed count availability.	No match found
Expression Atlas	Planned source for curated expression experiment links.	No match found
PubMed	Primary GEO citations and related PubMed articles that mention this dataset. 1 linked publication 1 DOI Primary publication TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation. Rheumatology (Oxford, England), 2022 PubMed DOI	Available

Metadata Quality Components

Persisted metadata quality

100 pts

Clarity: 100%
Weight: 100 pts

Sample source clarity: All samples have source metadata and clear GSE/GSM accessions. Group clarity: Rule-based grouping found both case and control samples. Disease clarity: Disease or condition metadata normalized. Tissue clarity: Anatomical source metadata normalized. Treatment clarity: No unclear treatment split detected in the sample metadata. Replicate clarity: No pooled sample or technical replicate flags detected. Data availability clarity: Dataset-level processed or raw data availability is explicit.

Analysis Readiness

Ready after review

100% DE readiness

Contrast completeness

25/25 pts

Both case and control groups are present in the proposed grouping.

Minimum group size

20/20 pts

Each contrast group has at least 2 samples.

Processed data availability

20/20 pts

Processed data is marked available in the GEO index.

Sample decision clarity

15/15 pts

All samples are assigned to a case or control group.

Blocking warnings

10/10 pts

No dataset warnings are present.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

No readiness blockers detected.

Next Steps

Verify the proposed sample assignments and case-versus-control comparison against the GEO metadata before using them in DESeq2 or another differential-expression tool.
Confirm processed count files and sample identifiers match the exported metadata.

Analysis Preparation Checklist

5/6 ready

Group labels reviewed

Needs review

Siftome proposed case and control labels, but no reviewer confirmation is stored yet.

Open the sample grouping CSV and confirm group labels before analysis.

Minimum sample count met

Ready

Both groups meet the minimum of 2 samples.

Confirm whether the cohort is large enough for the intended statistical analysis.

Processed counts available

Ready

Processed data availability is marked true in the GEO index.

Verify that downloaded processed files contain usable count or expression identifiers.

Ambiguous samples handled

Ready

No review-needed or unassigned samples are present in the proposed grouping.

Review the grouping table for biologically meaningful differences that the automated checks may not detect.

Exclusion decisions recorded

Ready

No hard-excluded samples were detected by the current rules.

Record any manual exclusions in the downstream analysis notes.

Source traceability preserved

Ready

The dataset and sample accessions can be traced back to GEO.

Keep GEO accessions with exported metadata.

Bioinformatician Review

Standard analyst review

Proceed only after the analyst confirms grouping, exclusions, and source files.

By Siftome standards, no expert review was triggered.

Why This Is Ranked Here

Tumor vs normal

Not suitable Dataset does not meet the current suitability threshold.

Applied Review Decisions

No active review decisions affect this ranking.

Derived Classifications

Disease context Rheumatoid arthritis Disease context came from Normalization rules.
Likely case group Knockdown 8 samples
Likely control group Genetic control 8 samples

Intent Interpretation

Downgrade or exclusion reason Downgraded for tissue search because it is a treatment/control experiment. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

Comparison: Treatment vs control. Specimen: Tissue. Comparison suitability: 0%.
Prioritized assay: bulk RNA-seq is the active assay expectation.
Interpreted disease metadata: Rheumatoid arthritis.
Processed data is available for downstream review.
External evidence: PubMed links 1 publication; 1 DOI available: PMID 35258553.
Publication context: TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation.. Rheumatology (Oxford, England), 2022. PMID 35258553. DOI 10.1093/rheumatology/keac124.

Cautions

Downgraded for tissue search because it is a treatment/control experiment.
Treatment/control experiment downgraded because this ranking targets tumor-vs-normal tissue comparisons.
Overall score capped because comparison suitability is weak for the selected search intent.
Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

No dataset warnings

Normalized Fields

28 fields

Field Value Source Derived by Confidence Evidence Reason

assay_type bulk RNA-seq GSE195557 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence bulk rna-seq dataset_accession: GSE195557 dataset_title: TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation organism: Homo sapiens assay_type: bu... keyword match keyword match: bulk rna-seq

control_type untreated control GSM5840489 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St1_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St1 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840491 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St2_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St2 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840492 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St2_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St2 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840494 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St1_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St1 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840496 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St3_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St3 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840497 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St3_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St3 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840500 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St4_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St4 controlled vocabulary controlled vocabulary control type match: sicontrol

control_type untreated control GSM5840501 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence sicontrol St4_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St4 controlled vocabulary controlled vocabulary control type match: sicontrol

disease rheumatoid arthritis GSE195557 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis dataset_accession: GSE195557 dataset_title: TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation organism: Homo sapiens assay_type: bu... controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840489 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St1_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St1 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840490 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St1_siTNFR2_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: TNF; patient: St1 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840491 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St2_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St2 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840492 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St2_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St2 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840493 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St2_siTNFR2_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: Control; patient: St2 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840494 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St1_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St1 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840495 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St2_siTNFR2_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: TNF; patient: St2 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840496 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St3_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St3 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840497 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St3_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St3 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840498 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St3_siTNFR2_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: Control; patient: St3 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840499 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St3_siTNFR2_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: TNF; patient: St3 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840500 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St4_sictrl_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: Control; patient: St4 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840501 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St4_sictrl_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siControl; treatment: TNF; patient: St4 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840502 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St4_siTNFR2_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: Control; patient: St4 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840503 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St4_siTNFR2_TNF Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: TNF; patient: St4 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

disease rheumatoid arthritis GSM5840504 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence rheumatoid arthritis St1_siTNFR2_ctrl Fibrobst-like synoviocytes tissue: Fibrobst-like synoviocytes; disease: Rheumatoid Arthritis; knockdown: siTNFR2; treatment: Control; patient: St1 controlled vocabulary controlled vocabulary disease match: rheumatoid arthritis

organism Homo sapiens GSE195557 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence homo sapiens dataset_accession: GSE195557 dataset_title: TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation organism: Homo sapiens assay_type: bu... keyword match keyword match: homo sapiens

tissue synovium GSE195557 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence synovial dataset_accession: GSE195557 dataset_title: TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation organism: Homo sapiens assay_type: bu... controlled vocabulary controlled vocabulary tissue match: synovial

Sample Group Preview

16 rows shown Show Hide

Study totals: Case 8 | Control 8 | Unassigned 0 | Excluded 0 | Ambiguous 0 16 rows shown

Group	Role	Accession	Title	Source / characteristics	Reason
Knockdown	Case	GSM5840490	St1_siTNFR2_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: TNF; Patient: St1	Genetic perturbation marker detected.
Knockdown	Case	GSM5840493	St2_siTNFR2_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: Control; Patient: St2	Genetic perturbation marker detected.
Knockdown	Case	GSM5840495	St2_siTNFR2_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: TNF; Patient: St2	Genetic perturbation marker detected.
Knockdown	Case	GSM5840498	St3_siTNFR2_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: Control; Patient: St3	Genetic perturbation marker detected.
Knockdown	Case	GSM5840499	St3_siTNFR2_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: TNF; Patient: St3	Genetic perturbation marker detected.
Knockdown	Case	GSM5840502	St4_siTNFR2_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: Control; Patient: St4	Genetic perturbation marker detected.
Knockdown	Case	GSM5840503	St4_siTNFR2_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: TNF; Patient: St4	Genetic perturbation marker detected.
Knockdown	Case	GSM5840504	St1_siTNFR2_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiTNFR2; Treatment: Control; Patient: St1	Genetic perturbation marker detected.
Genetic control	Control	GSM5840489	St1_sictrl_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: Control; Patient: St1	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840491	St2_sictrl_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: Control; Patient: St2	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840492	St2_sictrl_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: TNF; Patient: St2	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840494	St1_sictrl_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: TNF; Patient: St1	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840496	St3_sictrl_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: Control; Patient: St3	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840497	St3_sictrl_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: TNF; Patient: St3	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840500	St4_sictrl_ctrl	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: Control; Patient: St4	Genetic perturbation control marker detected.
Genetic control	Control	GSM5840501	St4_sictrl_TNF	Fibrobst-like synoviocytes Tissue: Fibrobst-like synoviocytes; Disease: Rheumatoid Arthritis; Knockdown: SiControl; Treatment: TNF; Patient: St4	Genetic perturbation control marker detected.

Use as Discovery Cohort

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Carry Siftome's disease, organism, specimen, assay, data type, and accession into a validation project. Uncertain fields remain Unknown.

Summary

Overall design

Source Evidence

Primary publication

Metadata Quality Components

Analysis Readiness

Blockers

Next Steps

Analysis Preparation Checklist

Bioinformatician Review

Why This Is Ranked Here

Applied Review Decisions

Derived Classifications

Intent Interpretation

Ranking Facts

Supporting evidence

Cautions

Dataset Warnings

Normalized Fields

Sample Group Preview

Use as Discovery Cohort