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pmid:36714107

Analysis of ferroptosis-associated genes in Crohn's disease based on bioinformatics.

Xingyu Ji · Su Ma · Xiaomei Sun · Dan Yu · Ye Song · Rui Li

Frontiers in medicine · 2022 doi:10.3389/fmed.2022.1058076

Paper

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Experiment

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Data

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title
Analysis of ferroptosis-associated genes in Crohn's disease based on bioinformatics.
doi
10.3389/fmed.2022.1058076
pmid
36714107
authors array · 6 items
[0]
Xingyu Ji
[1]
Su Ma
[2]
Xiaomei Sun
[3]
Dan Yu
[4]
Ye Song
[5]
Rui Li
journal
Frontiers in medicine
year
2022
abstract
Background: Ferroptosis, a novel mode of apoptosis has recently been shown to be associated with fibrosis, tumor, cardiovascular, and other diseases. In this study, using bioinformatic analysis, we identified ferroptosis genes associated with Crohn's disease (CD) and performed biological function analysis, identified potential drug targets, and provided new directions for the future treatment of CD. Methods: Differential expression analysis was performed using the GSE186582 dataset from the Gene Expression Omnibus (GEO) database. Ferroptosis-associated genes were downloaded from the FerrDB database, and overlapping genes associated with CD and ferroptosis were extracted. Then, we performed functional enrichment analysis, constructed a protein-protein interaction network (PPI), identified the correlation between hub genes and immune infiltration, performed external validation using a second and third dataset (GSE102133, GSE95095), and identified potential therapeutic agents. Finally, we validated the protein expression levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and healthy participants. Results: A total of 28 ferroptosis-associated genes associated with CD were identified in our analysis, which included 22 up-regulated and 6 down-regulated genes. Gene Ontology (GO) analysis showed that these genes are essential for the apical plasma membrane and amide transport, and Metascape analysis showed that these genes mainly act on IL-4 and IL-13 signaling pathways. Five hub genes, PTGS2, IL6, IL1B, NOS2, and IDO1, were identified by a protein interaction network, and external validation of these hub genes showed statistically significant differences in expression between the CD patients and normal participants (p < 0.05), and all AUC values were greater than 0.8. Further, we predicted the top 10 drugs used to treat CD. Immune infiltration results suggest that Hub gene is related to T cells, macrophages, dendritic cells, and other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expression of the hub gene was higher in CD colon tissue than in normal subjects (p < 0.05). Conclusion: Bioinformatics analysis showed that ferroptosis is closely related to the development of CD, and the prediction of potential drugs provides new targets for the treatment of CD. Moreover, five hub genes identified are potentially new and effective markers for the diagnosis of CD.
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For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis. Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis.
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sections[5] "2.3. Sample detection and differential gene analysis" paragraph 2
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For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis.
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sections[13] "2.11. Statistical analysis" paragraph 2
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Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
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Differential-expression analysis of GSE186582 identified 649 differentially expressed genes in Crohn’s disease colon tissues compared with normal human colon tissues, including 316 up-regulated and 333 down-regulated genes.
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We found 649 genes differentially expressed (p < 0.05 and |log2 FC| > 1) in the colon of CD patients tissues compared with normal human colon tissues, of which 316 genes were up-regulated and 333 genes were down-regulated as shown in the volcano plot (Figure 1B).
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sections[15] "3.1. Identification of differentially expressed genes" paragraph 2
quote
We found 649 genes differentially expressed (p < 0.05 and |log2 FC| > 1) in the colon of CD patients tissues compared with normal human colon tissues, of which 316 genes were up-regulated and 333 genes were down-regulated as shown in the volcano plot (Figure 1B).
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Differential-expression analysis of GSE186582 identified 649 differentially expressed genes in Crohn’s disease colon tissues compared with normal human colon tissues, including 316 up-regulated and 333 down-regulated genes.
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489
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null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Expression data from intestinal mucosa of patients with Crohn disease
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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data:geo:GSE95095
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note
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
structure object · 15 fields
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
access_statement_kind
data_availability_statement
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sample_count
60
group_sizes
null
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null
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14951
taxon
Homo sapiens
title
Differential Gene Expression between involved and uninvolved sites of Crohn’s disease: Insights into a Distinctive Pathogenesis Profile
resolution_checked_at
2026-11-01T18:06:44Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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false
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For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis. Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis.
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principal component analysis
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The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
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method.reader_differs_from_extractor
capability object · 3 fields
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candidate
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readiness object · 8 fields
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basis
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capability:computational_analysis
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owned
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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tier
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[0]
GSE186582
[1]
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[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.
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The paper names GSE186582, GSE102133, GSE95095 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
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minimax
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single_reader
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PMID 36714107 full text
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dataset
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Background: Ferroptosis, a novel mode of apoptosis has recently been shown to be associated wit
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paper_text_order:85
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ession levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and he
[1]
other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expressi
[2]
kage and GSEABase package. 2.10. Analysis of immunohistochemical results Immunohistochemical staining was per
[3]
.10. Analysis of immunohistochemical results Immunohistochemical staining was performed to validate the diffe
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to evaluate the immune cell infiltration of patients with Crohn’s disease in GSE186582 dataset. Subseq
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For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis. Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36714107", "kind": "science-record", "revision": 4, "content_hash": "sha256:1515a04515bf8f64730ccc39205eae7a57ee6211afb73636ddded618a2eb3eab", "created_at": "2026-11-01T19:01:17Z", "updated_at": "2026-11-01T22:51:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of ferroptosis-associated genes in Crohn's disease based on bioinformatics.", "doi": "10.3389/fmed.2022.1058076", "pmid": "36714107", "authors": ["Xingyu Ji", "Su Ma", "Xiaomei Sun", "Dan Yu", "Ye Song", "Rui Li"], "journal": "Frontiers in medicine", "year": 2022, "abstract": "Background: Ferroptosis, a novel mode of apoptosis has recently been shown to be associated with fibrosis, tumor, cardiovascular, and other diseases. In this study, using bioinformatic analysis, we identified ferroptosis genes associated with Crohn's disease (CD) and performed biological function analysis, identified potential drug targets, and provided new directions for the future treatment of CD.\nMethods: Differential expression analysis was performed using the GSE186582 dataset from the Gene Expression Omnibus (GEO) database. Ferroptosis-associated genes were downloaded from the FerrDB database, and overlapping genes associated with CD and ferroptosis were extracted. Then, we performed functional enrichment analysis, constructed a protein-protein interaction network (PPI), identified the correlation between hub genes and immune infiltration, performed external validation using a second and third dataset (GSE102133, GSE95095), and identified potential therapeutic agents. Finally, we validated the protein expression levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and healthy participants.\nResults: A total of 28 ferroptosis-associated genes associated with CD were identified in our analysis, which included 22 up-regulated and 6 down-regulated genes. Gene Ontology (GO) analysis showed that these genes are essential for the apical plasma membrane and amide transport, and Metascape analysis showed that these genes mainly act on IL-4 and IL-13 signaling pathways. Five hub genes, PTGS2, IL6, IL1B, NOS2, and IDO1, were identified by a protein interaction network, and external validation of these hub genes showed statistically significant differences in expression between the CD patients and normal participants (p < 0.05), and all AUC values were greater than 0.8. Further, we predicted the top 10 drugs used to treat CD. Immune infiltration results suggest that Hub gene is related to T cells, macrophages, dendritic cells, and other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expression of the hub gene was higher in CD colon tissue than in normal subjects (p < 0.05).\nConclusion: Bioinformatics analysis showed that ferroptosis is closely related to the development of CD, and the prediction of potential drugs provides new targets for the treatment of CD. Moreover, five hub genes identified are potentially new and effective markers for the diagnosis of CD.", "claims": [{"id": "claim-method", "statement": "For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis. Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36714107", "locator": "sections[5] \"2.3. Sample detection and differential gene analysis\" paragraph 2", "quote": "For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis."}, {"asset": "source:pmid:36714107", "locator": "sections[13] \"2.11. Statistical analysis\" paragraph 2", "quote": "Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36714107", "data:geo:GSE102133"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE102133"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:25:11Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14786, "completion_tokens": 2358, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36714107", "type": "paper", "label": "pmid:36714107"}, {"id": "source:pmid:36714107", "type": "manuscript", "label": "PMID 36714107 full text"}, {"id": "data:geo:GSE102133", "type": "dataset", "label": "GEO GSE102133"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36714107", "type": "paper", "label": "pmid:36714107"}, {"id": "source:pmid:36714107", "type": "manuscript", "label": "PMID 36714107 full text"}, {"id": "data:geo:GSE102133", "type": "dataset", "label": "GEO GSE102133"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36714107", "type": "extraction", "used": ["source:pmid:36714107"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE102133", "type": "accession_resolution", "used": ["data:geo:GSE102133"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36714107", "parent_hash": "sha256:77efce9c8f059c41d6ba31d1a98f3f3d7c1496dd07391af7b8cdc54003f0892a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE102133 licence not read", "asset:data:geo:GSE102133 not downloaded", "asset:data:geo:GSE186582 licence not read", "asset:data:geo:GSE186582 not downloaded", "asset:data:geo:GSE95095 licence not read", "asset:data:geo:GSE95095 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["Background: Ferroptosis, a novel mode of apoptosis has recently been shown to be associated wit"], "order_basis": "paper_text_order:85", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ession levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and he", "other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expressi", "kage and GSEABase package. 2.10. Analysis of immunohistochemical results Immunohistochemical staining was per", ".10. Analysis of immunohistochemical results Immunohistochemical staining was performed to validate the diffe"], "order_basis": "paper_text_order:1112", "id": "assay:2"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["to evaluate the immune cell infiltration of patients with Crohn’s disease in GSE186582 dataset. Subseq"], "order_basis": "paper_text_order:3181", "id": "assay:3"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["For principal component analysis (PCA), the two R packages FactoMineR and factoextra were used and the LIMMA package was used for differential gene expression analysis. Differences in hub genes expression in CD and healthy samples were calculated using the t-test, and correlation analysis were calculated using Spearman analysis."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}