GSE189136

Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients

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

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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.

Summary

Purpose: We analyzed RNA-seq from peripheral blood mononuclear cells (PBMC) in DMARDs-naïve RA patients and healthy subjects. Our goal was to evaluate the transcriptional profiles of ST2825-treated PBMC to identify its therapeutic potential. Methods: We analyzed bulk RNA-seq from peripheral blood mononuclear cells (PBMC) in DMARDs-naïve RA patients after stimulation with LPS and IL-1β, PBMC were treated with the MyD88 chemical inhibitor, ST2825. Collection of RNA was performed after 24 h of treatment and samples were sequenced to determine transcriptional changes and regulated processes in treated PBMC. Results: paired-end reads were mapped to the hg19 human genome assembly. RNA levels were normalized using DESeq. We identified 796 differentially expressed (DE) genes by 2-fold change (p<0.05) between RA patients and healthy subjects. Our analysis revealed 631 DE genes between DMARDs-naïve RA patients before and after ST2825 treatment. We identified 471 DE genes between LPS-stimulated RA PBMC and LPS-stimulated RA PBMC treated with ST2825. Conclusion: Our study provides comprehensive evidence supporting the potential application of the MyD88 inhibitor, ST2825, as a modulator of gene expression signtaures involved in pathogenic processes in PBMC from DMARDs-naïve RA patients. Our indepth analysis of RNA-seq data will serve as a valuable resource containing the inflammatory gene expression signatures by MyD88.

Overall design

Identification of the potential effect of ST2825 as an inhibitor of MyD88-dependent gene expression signatures to modulate inflammatory processes in RA patients.

Source Evidence

4 sources
Source Contribution Status
GEO

Original dataset metadata, sample metadata, source links, and GEO data availability flags.

Sample records
19 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

  1. Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients. Frontiers in pharmacology, 2021
Available

Metadata Quality Components

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 Treated 15 samples
  • Likely control group Untreated 4 samples

Intent Interpretation

  • Downgrade or exclusion reason Downgraded for tissue search because it is a biofluid cohort. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

  • Comparison: Treatment vs control. Specimen: Biofluid. 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 35002734.
  • Publication context: Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients.. Frontiers in pharmacology, 2021. PMID 35002734. DOI 10.3389/fphar.2021.800220.

Cautions

  • Downgraded for tissue search because it is a biofluid cohort.
  • Downgraded for tissue search because it is a treatment/control experiment.
  • Treatment/control experiment downgraded because this ranking targets tumor-vs-normal tissue comparisons.
  • Blood, plasma, or serum cohort downgraded because this ranking targets tissue tumor-vs-normal 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

101 fields

Sample Group Preview

19 rows shown
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Study totals: Case 15 | Control 4 | Unassigned 0 | Excluded 0 | Ambiguous 0 19 rows shown
Group Role Accession Title Source / characteristics Reason
Treated Case GSM5694896 PBMC_RA2_LPS PBMC Tissue: PBMC; Treatment: LPS; Diagnosis: Rheumatoid arthritis Treatment case marker detected.
Treated Case GSM5694897 PBMC_RA3_LPS PBMC Tissue: PBMC; Treatment: LPS; Diagnosis: Rheumatoid arthritis Treatment case marker detected.
Treated Case GSM5694898 PBMC_RA4_LPS PBMC Tissue: PBMC; Treatment: LPS; Diagnosis: Rheumatoid arthritis Treatment case marker detected.
Treated Case GSM5694899 PBMC_RA2_IL-1B PBMC Tissue: PBMC; Treatment: IL-1[beta]; Diagnosis: Rheumatoid arthritis Explicit characteristic comparison arm detected.
Treated Case GSM5694900 PBMC_RA3_IL-1B PBMC Tissue: PBMC; Treatment: IL-1[beta]; Diagnosis: Rheumatoid arthritis Explicit characteristic comparison arm detected.
Treated Case GSM5694901 PBMC_RA4_IL-1B PBMC Tissue: PBMC; Treatment: IL-1[beta]; Diagnosis: Rheumatoid arthritis Explicit characteristic comparison arm detected.
ST2825-treated Case GSM5694902 PBMC_RA2_ST2825 PBMC Tissue: PBMC; Treatment: ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694903 PBMC_RA3_ST2825 PBMC Tissue: PBMC; Treatment: ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694904 PBMC_RA4_ST2825 PBMC Tissue: PBMC; Treatment: ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694905 PBMC_RA2_LPS_ST2825 PBMC Tissue: PBMC; Treatment: LPS + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694906 PBMC_RA3_LPS_ST2825 PBMC Tissue: PBMC; Treatment: LPS + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694907 PBMC_RA4_LPS_ST2825 PBMC Tissue: PBMC; Treatment: LPS + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694908 PBMC_RA2_IL-1B_ST2825 PBMC Tissue: PBMC; Treatment: IL-1[beta] + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694909 PBMC_RA3_IL-1B_ST2825 PBMC Tissue: PBMC; Treatment: IL-1[beta] + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
ST2825-treated Case GSM5694910 PBMC_RA4_IL-1B_ST2825 PBMC Tissue: PBMC; Treatment: IL-1[beta] + ST2825; Diagnosis: Rheumatoid arthritis Treatment code resolved from the GEO Series design and sample label.
Untreated Control GSM5694892 PBMC_CS1_UTx PBMC Tissue: PBMC; Treatment: Untreated; Diagnosis: Healthy Treatment control marker detected.
Untreated Control GSM5694893 PBMC_CS4_UTx PBMC Tissue: PBMC; Treatment: Untreated; Diagnosis: Healthy Treatment control marker detected.
Untreated Control GSM5694894 PBMC_RA3_UTx PBMC Tissue: PBMC; Treatment: Untreated; Diagnosis: Rheumatoid arthritis Treatment control marker detected.
Untreated Control GSM5694895 PBMC_RA4_UTx PBMC Tissue: PBMC; Treatment: Untreated; Diagnosis: Rheumatoid arthritis Treatment control marker detected.

Use as Discovery Cohort

External Validation Finder

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