GSE171057

AI-guided use of balanced PPARα/g dual agonist finetunes macrophage responses in inflammatory bowel disease

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

31 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
Mus musculus
Whole-study samples
39 samples
Specimen
Tissue
Reported/interpreted study design
Treatment vs control Design classification does not establish patient pairs.
Comparison type
Tumor vs normal
Contributors
Sahoo D, Das S, Ghosh P
Contact name
Debashis Sahoo
Submission date
2021-03-29
Last update
2022-04-20
Organization
UCSD
Department
Pediatrics
Public date
2022-02-03
Experiment types
Expression profiling by high throughput sequencing
Platforms
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Series type
Series
SubSeries
Not available
BioProject
PRJNA718257

Summary

A computational platform, the Boolean network explorer (BoNE), has recently been developed to infuse AI-enhanced precision into drug discovery; it enables querying and navigating invariant Boolean Implication Networks of disease maps for prioritizing high-value targets. Here we used BoNE to query an Inflammatory Bowel Disease (IBD)-map and prioritize two nuclear receptors, PPARa/g. Balanced agonism of PPARa/g was predicted to impact macrophage processes, ameliorate colitis in network-prioritized animal models, ‘reset’ the gene expression network from disease to health, and achieve a favorable therapeutic index that tracked other FDA-approved targets. Predictions were validated using a balanced and potent PPARa/g-dual agonist (PAR5359) in two pre-clinical murine models, i.e., Citrobacter rodentium-induced infectious colitis and DSS-induced colitis. Mechanistically, we show that such balanced dual agonism promotes bacterial clearance more efficiently than individual agonists both in vivo and in vitro; PPARa is required and its agonism is sufficient to induce the pro-inflammatory cytokines and cellular ROS, which are essential for bacterial clearance and immunity, whereas PPARg-agonism blunts these responses, delays microbial clearance and induces the anti-inflammatory cytokine, IL10. Balanced agonism achieved controlled inflammation while protecting the gut barrier and ‘reversal’ of the transcriptomic network. Furthermore, dual agonism effectively reversed the defective bacterial clearance observed in PBMCs derived from IBD patients. These findings not only deliver a macrophage modulator for use as barrier-protective therapy in IBD, but also highlight the potential of BoNE to accelerate and enhance the precision of drug discovery.

Overall design

Mice were orally challenged with C. rodentium at 5 x 108 CFU in 0.1 ml of PBS. Distal colon samples were collected to assess histology and levels of mRNA (by qPCR and RNA Seq). PPARa agonist (GW7647, 20 ug/kg body weight/day), PPARg agonist (Pioglitazone, 20mg/kg body weight/day), PPARa/g dual agonist (PAR5359, 1 mg/kg body weight/day) were administered via intraperitoneal route in 200 ul total volume (DMSO less than 4%). Total RNA was isolated using TRIzol reagent (Life Technologies) and Quick-RNA MiniPrep Kit (Zymo Research, USA). Sequencing was performed.

Source Evidence

4 sources
Source Contribution Status
GEO

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

Sample records
39 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. Artificial intelligence-rationalized balanced PPARα/γ dual agonism resets dysregulated macrophage processes in inflammatory bowel disease. Communications biology, 2022
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: Treatment status metadata normalized where treatment is part of the comparison. Replicate clarity: No pooled sample or technical replicate flags detected. Data availability clarity: Dataset-level processed or raw data availability is explicit.

Analysis Readiness

Review before analysis
90% 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

0/10 pts

Critical warnings must be resolved before downstream analysis.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

  • Critical dataset warnings must be resolved.

Next Steps

  • Resolve critical warnings before downstream analysis.

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

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.

Critical dataset warnings are present.

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

  • Organism differs from search intent Mus musculus Search intent expects Homo sapiens. Organism came from Normalization rules.
  • Disease context Experimental colitis, inflammatory bowel disease Disease context came from Normalization rules.
  • Likely case group Treated 31 samples
  • Likely control group Untreated 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: Experimental colitis, Infectious disease or host response, Inflammatory bowel disease.
  • Processed data is available for downstream review.
  • External evidence: PubMed links 1 publication; 1 DOI available: PMID 35288651.
  • Publication context: Artificial intelligence-rationalized balanced PPARα/γ dual agonism resets dysregulated macrophage processes in inflammatory bowel disease.. Communications biology, 2022. PMID 35288651. DOI 10.1038/s42003-022-03168-4.

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.
  • Overall score capped because non-human datasets are outside the selected human ranking intent.
  • Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Normalized Fields

139 fields

Sample Group Preview

39 rows shown Show Hide
Study totals: Case 31 | Control 8 | Unassigned 0 | Excluded 0 | Ambiguous 0 39 rows shown
Group Role Accession Title Source / characteristics Reason
Treated Case GSM5217674 Citrobacter_7days_Uninf_1_S20 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: No; Infection: No Explicit characteristic comparison arm detected.
Treated Case GSM5217675 Citrobacter_7days_Uninf_2_S21 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: No; Infection: No Explicit characteristic comparison arm detected.
Treated Case GSM5217676 Citrobacter_7days_Uninf_3_S22 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: No; Infection: No Explicit characteristic comparison arm detected.
Treated Case GSM5217677 Citrobacter_7days_Uninf_4_S23 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: No; Infection: No Explicit characteristic comparison arm detected.
Treated Case GSM5217678 Citrobacter_7days_Uninf_5_S24 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: No; Infection: No Explicit characteristic comparison arm detected.
Treated Case GSM5217679 G13_Uninfected_1_S89_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: No; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217680 G14_Uninfected_2_S90_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: No; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217681 G15_Uninfected_3_S91_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: No; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217690 Citrobacter_7days_GW7647_1_S6 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217691 Citrobacter_7days_GW7647_2_S7 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217692 Citrobacter_7days_GW7647_3_S8 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217693 Citrobacter_7days_GW7647_4_S9 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217694 Citrobacter_7days_GW7647_5_S10 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217695 G4_Citrobacter_GW7647_1_S80_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217696 G5_Citrobacter_GW7647_2_S81_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217697 G6_Citrobacter_GW7647_3_S82_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: GW7647; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217698 Citrobacter_7days_Pioglitazone_1_S16 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217699 Citrobacter_7days_Pioglitazone_2_S17 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217700 Citrobacter_7days_Pioglitazone_3_S18 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217701 Citrobacter_7days_Pioglitazone_4_S19 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217702 G7_Citrobacter_Pioglitazone_1_S83_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217703 G8_Citrobacter_Pioglitazone_2_S84_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217704 G9_Citrobacter_Pioglitazone_3_S85_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: Pioglitazone; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217705 Citrobacter_7days_PAR5359_1_S11 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217706 Citrobacter_7days_PAR5359_2_S12 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217707 Citrobacter_7days_PAR5359_3_S13 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217708 Citrobacter_7days_PAR5359_4_S14 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217709 Citrobacter_7days_PAR5359_5_S15 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217710 G10_Citrobacter_PAR5359_1_S86_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217711 G11_Citrobacter_PAR5359_2_S87_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Treated Case GSM5217712 G12_Citrobacter_PAR5359_3_S88_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: PAR5359; Infection: Yes Explicit characteristic comparison arm detected.
Untreated Control GSM5217682 Citrobacter_7days_DMSO_1_S1 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217683 Citrobacter_7days_DMSO_2_S2 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217684 Citrobacter_7days_DMSO_3_S3 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217685 Citrobacter_7days_DMSO_4_S4 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217686 Citrobacter_7days_DMSO_5_S5 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 7; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217687 G1_Citrobacter_DMSO_1_S77_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217688 G2_Citrobacter_DMSO_2_S78_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: DMSO; Infection: Yes Treatment control marker detected.
Untreated Control GSM5217689 G3_Citrobacter_DMSO_3_S79_L003 Distal colon Strain: C57BL/6; Disease state: Inflammatory bowel disease; Tissue: Distal colon; Time: Day 18; Treatment: DMSO; Infection: Yes 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.