GSE193330

Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

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

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
12 samples
Specimen
Cell line
Reported/interpreted study design
Treatment vs control Design classification does not establish patient pairs.
Comparison type
Tumor vs normal
Contributors
Takayama K
Contact name
Kazuo Takayama
Submission date
2022-01-09
Last update
2023-06-06
Organization
Kyoto University
Department
Center for iPS Cell Research and Application
Public date
2023-03-07
Experiment types
Expression profiling by high throughput sequencing
Platforms
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Series type
Series
SubSeries
Not available
BioProject
PRJNA795800

Summary

SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.

Overall design

Total RNA was isolated from hepatocytes of uninfected or infected ibd- or bv-LoCs, and then RNA-seq was performed. At day 4 after the infection, total RNA was collected and RNA-seq was performed.

Source Evidence

4 sources
Source Contribution Status
GEO

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

Sample records
12 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. Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips. PNAS nexus, 2023
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

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

  • 12 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

12 review-needed samples and 0 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 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 COVID-19, inflammatory bowel disease Disease context came from Normalization rules.
  • Likely case group COVID-19 6 samples
  • Likely control group Control 6 samples

Intent Interpretation

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

Ranking Facts

Supporting evidence

  • Comparison: Treatment vs control. Specimen: Cell line. Comparison suitability: 0%.
  • Prioritized assay: bulk RNA-seq is the active assay expectation.
  • Interpreted disease metadata: COVID-19, 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 36896132.
  • Publication context: Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips.. PNAS nexus, 2023. PMID 36896132. DOI 10.1093/pnasnexus/pgad029.

Cautions

  • Downgraded for tissue search because it is a model-system experiment.
  • Downgraded for tissue search because it is a treatment/control experiment.
  • Excluded sample type flags reduce suitability.
  • Treatment/control experiment downgraded because this ranking targets tumor-vs-normal tissue comparisons.
  • Organoid or cell-line experiment downgraded for patient tissue search intent.
  • Excluded model-system sample markers reduce suitability.
  • 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

32 fields

Sample Group Preview

12 rows shown Show Hide
Study totals: Case 6 | Control 6 | Unassigned 0 | Excluded 0 | Ambiguous 0 12 rows shown
Group Role Accession Title Source / characteristics Reason
COVID-19 Case GSM5792288 Hepatocytes of SARS-CoV-2 infected ibd-LoC rep1 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
COVID-19 Case GSM5792289 Hepatocytes of SARS-CoV-2 infected ibd-LoC rep2 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
COVID-19 Case GSM5792290 Hepatocytes of SARS-CoV-2 infected ibd-LoC rep3 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
COVID-19 Case GSM5792294 Hepatocytes of SARS-CoV-2 infected bv-LoC rep1 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
COVID-19 Case GSM5792295 Hepatocytes of SARS-CoV-2 infected bv-LoC rep2 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
COVID-19 Case GSM5792296 Hepatocytes of SARS-CoV-2 infected bv-LoC rep3 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: SARS-CoV-2 infection cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792285 Hepatocytes of uninfected ibd-LoC rep1 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792286 Hepatocytes of uninfected ibd-LoC rep2 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792287 Hepatocytes of uninfected ibd-LoC rep3 Hepatocytes Cell line: HuCCT1; Cell type: Hepatocytes of ibd-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792291 Hepatocytes of uninfected bv-LoC rep1 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792292 Hepatocytes of uninfected bv-LoC rep2 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.
Control Control GSM5792293 Hepatocytes of uninfected bv-LoC rep3 Hepatocytes Cell line: HUVEC; Cell type: Hepatocytes of bv-LoC; Treatment: Control cell line: Standalone model-system marker retained for comparison grouping: cell line.

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.