GSE83381

Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [RNA-seq]

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

10 case / 0 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.

Summary

Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown. Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients. Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity.

Overall design

RNA-seq of 8 samples of peripheral blood derived mononuclear cells from CD patients having T/T or C/C genotype for rs6716753 SNP, with and without LPS treatment. 4 samples from healthy individuals with and without LPS treatment. RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours: siRNA mediated knockdown of SP140 versus controls. RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours for each condition: siRNA mediated knockdown of SP140 versus controls.

Source Evidence

4 sources
Source Contribution Status
GEO

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

Sample records
20 GSM samples
Primary source
recount3

Trusted source evidence for processed count availability.

recount3 project ID
srp076599
Available
Expression Atlas

Planned source for curated expression experiment links.

No match found
PubMed

Publication context when PubMed identifiers are already known.

No match found

Metadata Quality Components

Analysis Readiness

Review before analysis
85% 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

3/15 pts

Unassigned or review-needed samples remain before analysis.

Blocking warnings

7/10 pts

Warnings are present, but none are critical blockers.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

  • 4 samples are still unassigned.
  • 8 samples need manual grouping review.

Next Steps

  • Resolve unassigned or review-needed samples in the grouping table.

Analysis Preparation Checklist

4/6 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

Needs review

8 review-needed samples and 4 unassigned samples remain.

Resolve ambiguous and unassigned samples before finalizing the contrast.

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

Bioinformatician review required

Ask a bioinformatician to review grouping, count availability, exclusions, and design before DE.

Analysis readiness has blockers that must be resolved before DE.

One or more samples are unassigned and need manual grouping decisions.

One or more samples were flagged for manual review.

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 Crohn's disease Disease context came from Normalization rules.
  • Likely case group Crohn's disease 12 samples
  • Likely control group Control 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: Crohn's disease.
  • Processed data is available for downstream review.
  • External evidence: recount3 reports trusted processed count availability.

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

Normalized Fields

69 fields

Sample Group Preview

20 rows shown
Show Hide
Study totals: Case 10 | Control 0 | Unassigned 2 | Excluded 0 | Ambiguous 8 20 rows shown
Group Role Accession Title Source / characteristics Reason
Crohn's disease Case GSM2200449 CD T/T rep1 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: T/T rs6716753 Case marker detected.
Crohn's disease Case GSM2200450 CD C/C rep1 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Case marker detected.
Crohn's disease Case GSM2200451 CD T/T rep2 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: T/T rs6716753 Case marker detected.
Crohn's disease Case GSM2200452 CD C/C rep2 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Case marker detected.
Crohn's disease Case GSM2200453 CD T/T LPS+ rep1 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: T/T rs6716753 Case marker detected.
Crohn's disease Case GSM2200454 CD C/C LPS+ rep1 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Case marker detected.
Crohn's disease Case GSM2200455 CD T/T LPS+ rep2 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: T/T rs6716753 Case marker detected.
Crohn's disease Case GSM2200456 CD C/C LPS+ rep2 Peripheral blood derived mononuclear cells Disease state: Crohn's disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Case marker detected.
Treated Case GSM2200459 WT C/C LPS rep1 Peripheral blood derived mononuclear cells Disease state: Non-disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Treatment case marker detected.
Treated Case GSM2200460 WT C/C LPS rep2 Peripheral blood derived mononuclear cells Disease state: Non-disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 Treatment case marker detected.
Unassigned Unassigned GSM2200457 WT C/C rep1 Peripheral blood derived mononuclear cells Disease state: Non-disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 No explicit case or control marker detected.
Unassigned Unassigned GSM2200458 WT C/C rep2 Peripheral blood derived mononuclear cells Disease state: Non-disease; Cell type: Peripheral blood derived mononuclear cells; Genotype: C/C rs6716753 No explicit case or control marker detected.
Control Ambiguous GSM2344751 Donor 1 control 0h Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: None ambiguous sample: Ambiguous case/control metadata detected.
Unassigned Ambiguous GSM2344752 Donor 1 SP140 KD 0h Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: SP140 ambiguous sample: Ambiguous case/control metadata detected.
Control Ambiguous GSM2344753 Donor 1 control 4h LPS Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: None ambiguous sample: Ambiguous case/control metadata detected.
Treated Ambiguous GSM2344754 Donor 1 SP140 KD 4h LPS Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: SP140 ambiguous sample: Ambiguous case/control metadata detected.
Control Ambiguous GSM2344755 Donor 2 control 0h Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: None ambiguous sample: Ambiguous case/control metadata detected.
Unassigned Ambiguous GSM2344756 Donor 2 SP140 KD 0h Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: SP140 ambiguous sample: Ambiguous case/control metadata detected.
Control Ambiguous GSM2344757 Donor 2 control 4h LPS Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: None ambiguous sample: Ambiguous case/control metadata detected.
Treated Ambiguous GSM2344758 Donor 2 SP140 KD 4h LPS Peripheral blood Disease status: Unknown; Cell type: PBMC derived macrophage; Sirna: SP140 ambiguous sample: Ambiguous case/control metadata 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.