Development and Experimental Validation of Machine Learning-Based Disulfidptosis-Related Ferroptosis Biomarkers in Inflammatory Bowel Disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40428318", "kind": "science-record", "revision": 3, "content_hash": "sha256:cf17719e06c64e7a5a68f9e91ce0ac5d9ae8b3b513d82bbc55e8911990f7042e", "created_at": "2026-11-01T20:30:34Z", "updated_at": "2026-11-01T22:14:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and Experimental Validation of Machine Learning-Based Disulfidptosis-Related Ferroptosis Biomarkers in Inflammatory Bowel Disease.", "doi": "10.3390/genes16050496", "pmid": "40428318", "authors": ["Yongchao Liu", "Jing Shao", "Jie Zhang", "Mengmeng Sang", "Qiuyun Xu", "Liming Mao"], "journal": "Genes", "year": 2025, "abstract": "Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, defined by intestinal epithelial cell death. While ferroptosis and disulfidptosis have been linked to IBD pathogenesis, the functional significance of disulfidptosis-related ferroptosis genes (DRFGs) in this disease remains poorly characterized. This investigation sought to pinpoint DRFGs as diagnostic indicators and clarify their mechanistic contributions to IBD progression. Methods: Four IBD datasets (GSE65114, GSE87473, GSE102133, and GSE186582) from the GEO database were integrated to identify differentially expressed genes (DEGs) (|log2FC| > 0.585, adj. p < 0.05). A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs. The immune subtypes and single-cell sequencing (GSE217695) results were analyzed. A DSS-induced colitis Mus musculus (C57BL/6) model was used for validation. Results: Transcriptomic profiling identified 521 DEGs, with 16 defined as DRFGs. Nine hub genes showed diagnostic potential (AUC: 0.71-0.91). Functional annotation demonstrated that IBD-associated genes regulate diverse pathways, with a network analysis revealing their functional synergy. The PPI networks prioritized DUOX2, NCF2, ACSL4, GPX2, CBS, and LPCAT3 as central hubs. Two immune subtypes exhibited divergent DRFG expression. Single-cell mapping revealed epithelial/immune compartment specificity. The DSS-induced murine colitis model confirmed differential expression patterns of DRFGs, with concordant results between qRT-PCR and RNA-seq, emphasizing their pivotal regulatory roles in disease progression and potential for translational application. Conclusions: DRFGs mediate IBD progression via multi-signal pathway regulation across intestinal cell types, demonstrating diagnostic and prognostic potential.", "claims": [{"id": "claim-method", "statement": "A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40428318", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40428318", "locator": "sections[37] \"Data Availability Statement\" paragraph 2", "quote": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Nine hub genes showed diagnostic potential (AUC: 0.71–0.91).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40428318", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Nine hub genes showed diagnostic potential (AUC: 0.71–0.91)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Nine hub genes showed diagnostic potential (AUC: 0.71–0.91).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40428318"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102133"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102133"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40428318", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/genes16050496", "sha256": "sha256:66bc24d95ca0ef9d2efb609d80aff3e38bde56c7b72cf83d9139368fb83363e1", "bytes": 60087, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/genes16050496", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12110833", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102133", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102133", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102133", "version": null, "note": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2728650", "GSM2728651", "GSM2728652", "GSM2728653", "GSM2728654", "GSM2728655", "GSM2728656", "GSM2728657", "GSM2728658", "GSM2728659", "GSM2728660", "GSM2728661", "GSM2728662", "GSM2728663", "GSM2728664", "GSM2728665", "GSM2728666", "GSM2728667", "GSM2728668", "GSM2728669", "GSM2728670", "GSM2728671", "GSM2728672", "GSM2728673", "GSM2728674", "GSM2728675", "GSM2728676", "GSM2728677", "GSM2728678", "GSM2728679", "GSM2728680", "GSM2728681", "GSM2728682", "GSM2728683", "GSM2728684", "GSM2728685", "GSM2728686", "GSM2728687", "GSM2728688", "GSM2728689", "GSM2728690", "GSM2728691", "GSM2728692", "GSM2728693", "GSM2728694", "GSM2728695", "GSM2728696", "GSM2728697", "GSM2728698", "GSM2728699", "GSM2728700", "GSM2728701", "GSM2728702", "GSM2728703", "GSM2728704", "GSM2728705", "GSM2728706", "GSM2728707", "GSM2728708", "GSM2728709", "GSM2728710", "GSM2728711", "GSM2728712", "GSM2728713", "GSM2728714", "GSM2728715", "GSM2728716", "GSM2728717", "GSM2728718", "GSM2728719", "GSM2728720", "GSM2728721", "GSM2728722", "GSM2728723", "GSM2728724", "GSM2728725", "GSM2728726"], "sample_count": 77, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Mucosal gene expression profiling in ileum of patients with Crohn's disease", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE186582", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186582", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE186582", "version": null, "note": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). 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Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. 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Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. 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Computational scripts generated during this research are available upon formal request to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1587517", "GSM1587518", "GSM1587519", "GSM1587520", "GSM1587521", "GSM1587522", "GSM1587523", "GSM1587524", "GSM1587525", "GSM1587526", "GSM1587527", "GSM1587528", "GSM1587529", "GSM1587530", "GSM1587531", "GSM1587532", "GSM1587533", "GSM1587534", "GSM1587535", "GSM1587536", "GSM1587537", "GSM1587538", "GSM1587539", "GSM1587540", "GSM1587541", "GSM1587542", "GSM1587543", "GSM1587544"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "16686", "taxon": "Homo sapiens", "title": "Expression data from colonic mucosal biopsies from healthy controls and patients with active ulcerative colitis", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE87473", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87473", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE87473", "version": null, "note": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). 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127, "group_sizes": null, "group_sizes_basis": null, "platform": "13158", "taxon": "Homo sapiens", "title": "Gene expression profiling of mucosal biopsies from pediatric or adult patients with moderately to severely active ulcerative colitis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE102133 not downloaded", "asset:data:geo:GSE102133 licence not read", "asset:data:geo:GSE186582 not downloaded", "asset:data:geo:GSE186582 licence not read", "asset:data:geo:GSE217695 not downloaded", "asset:data:geo:GSE217695 licence not read", "asset:data:geo:GSE65114 not downloaded", "asset:data:geo:GSE65114 licence not read", "asset:data:geo:GSE87473 not downloaded", "asset:data:geo:GSE87473 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": 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{"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE65114", "GSE87473", "GSE102133", "GSE186582", "GSE217695"], "resolved_accessions": ["GSE65114", "GSE87473", "GSE102133", "GSE186582", "GSE217695"], "statements": ["The datasets and Supplementary Materials supporting this investigation are available within the published article and associated resources. Additional requests for data access may be submitted to the lead investigators. Transcriptomic profiles were sourced from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/; accessed 1 October 2024), incorporating four datasets (GSE65114, GSE87473, GSE102133, and GSE186582) and single-cell RNA-seq data (GSE217695). Computational scripts generated during this research are available upon formal request to the corresponding authors."], "basis": "The paper names GSE65114, GSE87473, GSE102133, GSE186582, GSE217695 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:40428318", "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": "2026-11-01T19:53:25Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17116, "completion_tokens": 2045, "cached_tokens": 256}}, "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:40428318", "type": "paper", "label": "pmid:40428318"}, {"id": "source:pmid:40428318", "type": "manuscript", "label": "PMID 40428318 full text"}, {"id": "data:geo:GSE102133", "type": "dataset", "label": "GEO GSE102133"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40428318", "type": "paper", "label": "pmid:40428318"}, {"id": "source:pmid:40428318", "type": "manuscript", "label": "PMID 40428318 full text"}, {"id": "data:geo:GSE102133", "type": "dataset", "label": "GEO GSE102133"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40428318", "type": "extraction", "used": ["source:pmid:40428318"], "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:40428318", "parent_hash": "sha256:675a3f0129165571a16d3c7141fb26dbc4b670965cc87c1c606561ece247d691", "fork_of": null, "generation": 2}, "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:GSE217695 licence not read", "asset:data:geo:GSE217695 not downloaded", "asset:data:geo:GSE65114 licence not read", "asset:data:geo:GSE65114 not downloaded", "asset:data:geo:GSE87473 licence not read", "asset:data:geo:GSE87473 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["with concordant results between qRT-PCR and RNA-seq, emphasizing their pivotal regulatory roles", "L/6) model was used for validation. Results: Transcriptomic profiling identified 521 DEGs, with 16 defin", "constituent (Supplementary Figure S1B). The transcriptomic profiles of the control group exhibited sign"], "order_basis": "paper_text_order:1105", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["une compartment specificity. The DSS-induced murine colitis model confirmed differential express", "for all experimental subjects. Male C57BL/6 mice were randomly allocated to two cohorts s (n = 4 p", "owing an established protocol [19]. Finally, mice were euthanized in a carbon dioxide chamber. The"], "order_basis": "paper_text_order:1619", "id": "assay:2"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}