GSE150734

Prognostic Liver Signature profiles in biopsy tissues from non-alcoholic fatty liver disease (NAFLD) patients in the U.S.

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

309 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

Background/Aims: There is a major unmet need to assess prognostic impact of anti-fibrotics in clinical trials due to the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. Methods: A Fibrosis Progression Signature (FPS) was defined to predict fibrosis progression within 5 years in HCV and NAFLD patients with no to minimal fibrosis at baseline (n=421), and validated in an independent NAFLD cohort (n=78). The FPS was used to assess response to 13 candidate anti-fibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n=78), and cenicriviroc in NASH patients enrolled in a clinical trial (n=19, NCT02217475). A serum-protein-based surrogate FPS (FPSec) was developed and technically evaluated in a liver disease patient cohort (n=79). Results: A 20-gene FPS was defined and validated in an independent NAFLD cohort (aOR=10.93, AUROC=0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacological target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate anti-fibrotics identified rational combination therapies based on epigallocatechin gallate, some of which were validated for enhanced anti-fibrotic effect in ex vivo culture of clinical liver tissues. In NASH patients treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of PPARalpha pathway was absent in patients without fibrosis improvement, suggesting benefit of combining PPARalpha agonism to improve anti-fibrotic efficacy of cenicriviroc. A 7-protein FPSec panel showed concordant prognostic prediction with FPS. Conclusion: FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform anti-fibrotic drug development.

Overall design

Gene expression profiling of formalin-fixed paraffin-embedded liver biopsy tissues. The samples for the FPS derivation set 4.

Source Evidence

4 sources
Source Contribution Status
GEO

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

Sample records
309 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. Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development. Gastroenterology, 2022
Available

Metadata Quality Components

Analysis Readiness

Not ready
55% DE readiness

Contrast completeness

10/25 pts

Only one side of the contrast is present; downstream DE needs both groups.

Minimum group size

0/20 pts

Minimum group size cannot be evaluated until a complete contrast exists.

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

  • No complete case/control contrast is available.
  • Critical dataset warnings must be resolved.

Next Steps

  • Resolve critical warnings before downstream analysis.

Analysis Preparation Checklist

4/6 ready

Group labels reviewed

Blocked

No complete case/control grouping exists yet.

Review the sample grouping table and assign both case and control groups.

Minimum sample count met

Blocked

At least one group has fewer than 2 samples.

Choose a larger dataset or merge only scientifically valid groups.

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.

Analysis preparation checklist contains blocked items.

No complete case/control or treatment/control contrast is available.

At least one comparison group has fewer than two samples.

Critical dataset warnings are present.

Assay context may require expert handling before DESeq2-style analysis.

Study design is model-system or unclear and should be reviewed before analysis.

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

  • Assay differs from search intent Microarray Search intent expects bulk RNA-seq. Assay came from Normalization rules.
  • Disease context Alcoholic liver disease, fibrosis, liver fibrosis, steatohepatitis, steatotic liver disease Disease context came from Normalization rules.
  • Likely case group Liver fibrosis 309 samples
  • Likely control group No control group detected 0 samples

Intent Interpretation

  • Downgrade or exclusion reason Comparison: Unclear study design. Specimen: Unclear specimen/source. Comparison suitability: 0%. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

  • Interpreted disease metadata: Alcoholic liver disease, Fibrosis, Liver fibrosis, Steatohepatitis (NASH/MASH), Steatotic liver disease (NAFLD/MASLD).
  • Processed data is available for downstream review.
  • External evidence: PubMed links 1 publication; 1 DOI available: PMID 34951993.
  • Publication context: Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.. Gastroenterology, 2022. PMID 34951993. DOI 10.1053/j.gastro.2021.12.250.

Cautions

  • Comparison: Unclear study design. Specimen: Unclear specimen/source. Comparison suitability: 0%.
  • Downgraded for tissue search because study design or specimen source is unclear.
  • Downgraded assay: microarray cohorts are separated from the RNA-seq intent.
  • Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Missing or unclear metadata. Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Unclear specimen/source downgraded for patient tissue tumor-vs-normal search intent.
  • Missing or unclear metadata. Unclear specimen/source downgraded for patient tissue tumor-vs-normal search intent.
  • Overall score capped because comparison suitability is weak for the selected search intent.
  • Missing or unclear metadata. Comparison - Unclear study design. Specimen - Unclear specimen/source. Comparison suitability: 0%.
  • Missing or unclear metadata. Downgraded for tissue search because study design or specimen source is unclear.
  • Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Normalized Fields

showing 500 of 626 fields

Sample Group Preview

showing 50 of 309 preview rows
Show Hide
Study totals: Case 309 | Control 0 | Unassigned 0 | Excluded 0 | Ambiguous 0 showing 50 of 309 preview rows
Group Role Accession Title Source / characteristics Reason
Liver fibrosis Case GSM4557370 AW13_WCA393 AW13_WCA393 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557371 AW14_WCA390 AW14_WCA390 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557372 AW15_WCA386 AW15_WCA386 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557373 AW16_WCA234 AW16_WCA234 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557374 AW17_WCA136 AW17_WCA136 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557375 AW18_WCA129 AW18_WCA129 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557376 AW19_WCA396 AW19_WCA396 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557377 AW20_WCA367 AW20_WCA367 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557378 AW21_WCA155 AW21_WCA155 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557379 AW22_WCA319 AW22_WCA319 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557380 AW23_WCA315 AW23_WCA315 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557381 AW24_WCA305 AW24_WCA305 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557382 AW25_WCA395 AW25_WCA395 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557383 AW26_WCA370 AW26_WCA370 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557384 AW27_WCA201 AW27_WCA201 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557385 AW28_WCA179 AW28_WCA179 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557386 AW29_WCA126 AW29_WCA126 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557387 AW30_WCA009 AW30_WCA009 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557388 AW31_WCA369 AW31_WCA369 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557389 AW34_WCA384 AW34_WCA384 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557390 AW37_WCA140 AW37_WCA140 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557391 AW38_WCA161 AW38_WCA161 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557392 AW40_WCA185 AW40_WCA185 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557393 AW41_WCA094 AW41_WCA094 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557394 AW42_WCA204 AW42_WCA204 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557395 AW45_WCA171 AW45_WCA171 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557396 AW46_WCA183 AW46_WCA183 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557397 AW47_WCA018 AW47_WCA018 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557398 AW48_WCA089 AW48_WCA089 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557399 AW49_WCA092 AW49_WCA092 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557400 AW50_WCA080 AW50_WCA080 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557401 AW51_WCA093 AW51_WCA093 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557402 AW52_WCA063 AW52_WCA063 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557403 AW53_WCA053 AW53_WCA053 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557404 AW54_WCA013 AW54_WCA013 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557405 AW55_WCA127 AW55_WCA127 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557406 AW56_WCA168 AW56_WCA168 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557407 AW58_WCA145 AW58_WCA145 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557408 AW59_WCA078 AW59_WCA078 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557409 AW60_STM437 AW60_STM437 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557410 AW62_STM296 AW62_STM296 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557411 AW63_STM422 AW63_STM422 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557412 AW64_STM438 AW64_STM438 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557413 AW65_STM273 AW65_STM273 Fibrosis stage: 1; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557414 AW66_STM266 AW66_STM266 Fibrosis stage: 1; Pls risk prediction: Low Case marker detected.
Liver fibrosis Case GSM4557415 AW68_STM417 AW68_STM417 Fibrosis stage: 1; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557416 AW69_WCA198 AW69_WCA198 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557417 AW70_WCA186 AW70_WCA186 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
Liver fibrosis Case GSM4557418 AW71_WCA135 AW71_WCA135 Fibrosis stage: 0; Pls risk prediction: High Case marker detected.
Liver fibrosis Case GSM4557419 AW72_WCA334 AW72_WCA334 Fibrosis stage: 0; Pls risk prediction: Intermediate Case marker detected.
259 additional case samples are hidden from this preview.

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.