GSE15934

Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP

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

2 case / 2 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: microarray
Organism: Homo sapiens
Whole-study samples: 4 samples
Specimen: Tissue
Reported/interpreted study design: Disease/model vs control Design classification does not establish patient pairs.

Comparison type: Tumor vs normal
Contributors: Rieder F, West GA, de la Motte C, Gopalan B, Fiocchi C
Contact name: Florian Rieder
Submission date: 2009-05-02
Last update: 2013-01-18
Organization: Cleveland Clinic
Department: Dept of Pathobiology
Public date: 2011-11-02
Experiment types: Expression profiling by array
Platforms: GPL6104 Illumina humanRef-8 v2.0 expression beadchip
Series type: SubSeries
SubSeries: Not available
BioProject: PRJNA123047

Summary

Intestinal fibrosis is a well-known complication of inflammatory bowel disease (IBD) and has important clinical implications for both forms of IBD, Crohn's disease (CD) and ulcerative colitis (UC). In addition to mesenchymal cells, endothelial cell contribute to organ fibrosis through the process of endothelial-to-mesenchymal transition (EndoMT). Our aim was to investigate if human intestinal microvascular endothelial cells (HIMEC) can undergo EndoMT, produce extracellular matrix, and contribute to fibrosis in both forms of IBD. Cellular transformation is a highly complex event involving drastic changes in multiple gene expression levels. To assess global genomic changes accompanying HIMEC transformation, we performed microarray analysis comparing transformed to non-transformed/untreated HIMEC. Consistent with the morphological, phenotypic and functional findings, transformed HIMEC downregulated the expression levels of genes typically expressed in endothelial cells and upregulated several genes of ECM molecules known to be increased in intestinal fibrosis. Thus, it is evident that inflammatory stimuli induce transdifferentiation of HIMEC into matrix-producing mesenchymal cells. Because the conditions inducing transformation in vitro reproduce those found in vivo during active gut inflammation, the microvasculature may contribute to IBD-associated fibrosis through the novel process of EndoMT. This series includes all treated or TRANSFORMED HIMEC samples (4).

Overall design

Surgically resected specimens were used for isolation of human intestinal microvascular endothelial cells (HIMEC). HIMEC monolayers derived from intestinal mucosa of four different subjects – 2 controls, 1 ulcerative colitis, and 1 crohns were cultured in 75cm2 tissue culture flasks coated with fibronectin. Cells were left untreated (unstimulated/non-transformed) or exposed to the combination of IL-1b 100 U/ml, TNF-a 100 U/ml and TGF-b1, 5ng/ml (TGFTNFIL1) for six days. HIMEC medium was changed every 3 days. Total ribonucleic acid (RNA) was extracted using a commercially available kit (Qiagen®). RNA was reverse transcribed into cRNA which was then hybridized to the Illumina HumanRef-8 v2 Expression BeadChip. The raw gene expression datasets were processed to remove outliers, log2 transformed and quantile normalized using R lumi software. Those genes that satisfied the FDR p-value threshold of < 0.05 or raw p-value of <0.001 were identified as significant for the functional pathway and network analysis.

Source Evidence

4 sources

Source	Contribution	Status
GEO	Original dataset metadata, sample metadata, source links, and GEO data availability flags. Sample records 4 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	Publication context when PubMed identifiers are already known.	No match found

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

Ready after review

97% 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

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

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

Bioinformatician review required

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

Small cohort warning is present.

Assay context may require expert handling before DESeq2-style 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 Crohn's disease, fibrosis, inflammatory bowel disease, ulcerative colitis Disease context came from Normalization rules.
Likely case group Ulcerative colitis 2 samples
Likely control group Healthy control 2 samples

Intent Interpretation

Downgrade or exclusion reason Downgraded assay: microarray cohorts are separated from the RNA-seq intent. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

Comparison: Disease/model vs control. Specimen: Tissue. Comparison suitability: 0%.
Interpreted disease metadata: Crohn's disease, Fibrosis, Inflammatory bowel disease, Ulcerative colitis.
Processed data is available for downstream review.

Cautions

Downgraded assay: microarray cohorts are separated from the RNA-seq intent.
Disease/control design without a tumor/normal comparison is outside tumor/normal triage.
Microarray expression context downgraded below primary bulk RNA-seq for the default tissue ranking.
Overall score capped because comparison suitability is weak for the selected search intent.
Overall score capped because fewer than six samples are too small for top-ranked cohort confidence.
Overall score capped because microarray cohorts should be compared separately from RNA-seq cohorts.
Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Dataset has fewer than six samples and should not be treated as a high-confidence cohort without manual review.
Microarray expression context was detected; compare separately from RNA-seq cohorts.
Multiple disease or phenotype arms were detected. The displayed grouping summarizes the full dataset; select the requested disease-specific contrast before analysis.
Microarray datasets are downgraded in the patient-tissue tumor-normal intent unless secondary assays are explicitly enabled.

Normalized Fields

15 fields

Field Value Source Derived by Confidence Evidence Reason

assay_type microarray GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence microarray dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... keyword match keyword match: microarray

disease Crohn's disease GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence Crohn's disease dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... controlled vocabulary controlled vocabulary disease match: Crohn's disease

disease fibrosis GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence fibrosis dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... controlled vocabulary controlled vocabulary disease match: fibrosis

disease inflammatory bowel disease GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence inflammatory bowel disease dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... controlled vocabulary controlled vocabulary disease match: inflammatory bowel disease

disease ulcerative colitis GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence ulcerative colitis dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... controlled vocabulary controlled vocabulary disease match: ulcerative colitis

disease ulcerative colitis GSM399770 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence ulcerative colitis HIMEC ulcerative colitis TGFTNFIL1 12h human intestinal microvascular endothelial cells, ulcerative colitis patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal muco... controlled vocabulary controlled vocabulary disease match: ulcerative colitis

disease Crohn's disease GSM399771 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence Crohn's disease HIMEC Crohn's disease TGFTNFIL1 12h human intestinal microvascular endothelial cells, crohn’s disease patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; ge... controlled vocabulary controlled vocabulary disease match: Crohn's disease

organism Homo sapiens GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED high confidence homo sapiens dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... keyword match keyword match: homo sapiens

sample_type normal tissue GSM399769 Runtime Siftome inference UNRESOLVED / UNREVIEWED low confidence normal HIMEC normal 1 TGFTNFIL1 12h human intestinal microvascular endothelial cells, control patient 1, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; gender: Male; a... controlled vocabulary controlled vocabulary sample type match: normal

sample_type normal tissue GSM399772 Runtime Siftome inference UNRESOLVED / UNREVIEWED low confidence normal HIMEC normal 2 TGFTNFIL1 12h human intestinal microvascular endothelial cells, control patient 2, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; gender: Male; a... controlled vocabulary controlled vocabulary sample type match: normal

tissue intestine GSE15934 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence intestinal dataset_accession: GSE15934 dataset_title: Analysis of Gene Expression changes in human intestinal endothelial-to-mesenchymal transition - TRANSFORMED GROUP organism: Homo sapie... controlled vocabulary controlled vocabulary tissue match: intestinal

tissue intestine GSM399769 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence intestinal HIMEC normal 1 TGFTNFIL1 12h human intestinal microvascular endothelial cells, control patient 1, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; gender: Male; a... controlled vocabulary controlled vocabulary tissue match: intestinal

tissue intestine GSM399770 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence intestinal HIMEC ulcerative colitis TGFTNFIL1 12h human intestinal microvascular endothelial cells, ulcerative colitis patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal muco... controlled vocabulary controlled vocabulary tissue match: intestinal

tissue intestine GSM399771 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence intestinal HIMEC Crohn's disease TGFTNFIL1 12h human intestinal microvascular endothelial cells, crohn’s disease patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; ge... controlled vocabulary controlled vocabulary tissue match: intestinal

tissue intestine GSM399772 Runtime Siftome inference UNRESOLVED / UNREVIEWED medium confidence intestinal HIMEC normal 2 TGFTNFIL1 12h human intestinal microvascular endothelial cells, control patient 2, TGFbeta1/TNFalpha/IL-1beta, 12 hours tissue: Intestinal mucosa; gender: Male; a... controlled vocabulary controlled vocabulary tissue match: intestinal

Sample Group Preview

4 rows shown Show Hide

Study totals: Case 2 | Control 2 | Unassigned 0 | Excluded 0 | Ambiguous 0 4 rows shown

Group	Role	Accession	Title	Source / characteristics	Reason
Ulcerative colitis	Case	GSM399770	HIMEC ulcerative colitis TGFTNFIL1 12h	Human intestinal microvascular endothelial cells, ulcerative colitis patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours Tissue: Intestinal mucosa; Gender: Female; Age: 34 yrs; Disease state: Ulcerative colitis	Case marker detected.
Crohn's disease	Case	GSM399771	HIMEC Crohn's disease TGFTNFIL1 12h	Human intestinal microvascular endothelial cells, crohn’s disease patient, TGFbeta1/TNFalpha/IL-1beta, 12 hours Tissue: Intestinal mucosa; Gender: Male; Age: 37 yrs; Disease state: Crohn's disease	Case marker detected.
Healthy control	Control	GSM399769	HIMEC normal 1 TGFTNFIL1 12h	Human intestinal microvascular endothelial cells, control patient 1, TGFbeta1/TNFalpha/IL-1beta, 12 hours Tissue: Intestinal mucosa; Gender: Male; Age: 56 yrs; Disease state: Normal	Sample-local control marker detected.
Healthy control	Control	GSM399772	HIMEC normal 2 TGFTNFIL1 12h	Human intestinal microvascular endothelial cells, control patient 2, TGFbeta1/TNFalpha/IL-1beta, 12 hours Tissue: Intestinal mucosa; Gender: Male; Age: 48 yrs; Disease state: Normal	Sample-local 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.