Exploring the molecular characteristics of inflammatory bowel disease from the perspective of hypoxia-related genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40771912", "kind": "science-record", "revision": 4, "content_hash": "sha256:0c3aac72b5cf1efbbcea7ba71b1af38cef8b5d895b18002c21ab44f1a3565f97", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:56:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the molecular characteristics of inflammatory bowel disease from the perspective of hypoxia-related genes.", "doi": "10.3389/fphar.2025.1612676", "pmid": "40771912", "authors": ["Lei Zheng", "Lin Mou", "Lingying Hao", "Rui Chen", "Yifei Wang", "Miao Yu", "Xueyan Zhang"], "journal": "Frontiers in pharmacology", "year": 2025, "abstract": "Background: Inflammatory bowel disease (IBD) constitutes a chronic inflammatory disorder affecting the gastrointestinal tract, characterized by a multifaceted pathogenesis that encompasses genetic, environmental, and immunological influences. The role of hypoxia in IBD pathophysiology has been recognized. However, the specific genes associated with hypoxia and their potential for diagnostic application remain inadequately investigated.\nMethods: Three datasets (GSE48958, GSE75214, and GSE179285) were procured from the Gene Expression Omnibus (GEO) database through the GEOquery package, all sourced from human colon tissue. Hypoxia-related genes (HRGs) were extracted from the GeneCards database. Data preprocessing involved mitigating batch effects via the sva package and normalizing with the limma package. The differential expression analysis, conducted with limma, uncovered 475 differentially expressed genes (DEGs), comprising 152 downregulated and 323 upregulated genes. A subset of 23 hypoxia-related differentially expressed genes (HRDEGs), including ADM, BHLHE40, CCL2, and CD274, was identified by intersecting DEGs with HRG sets.\nResults: The analysis identified 475 DEGs within the aggregated dataset, with 323 exhibiting upregulation and 152 downregulation. Enrichment analysis highlighted the significant role of these HRDEGs in critical processes such as angiogenesis and the HIF-1 signaling pathway. A diagnostic model (DM) integrating 13 HRDEGs exhibited high accuracy, achieving an area under the curve (AUC) exceeding 0.9 across various datasets. Immune infiltration analysis revealed substantial disparities in 13 distinct immune cell populations when comparing high-risk and low-risk cohorts.\nConclusions: In summary, this investigation underscores the pivotal function of HRGs in IBD's pathogenesis and introduces a reliable DM grounded in these genetic factors. The findings accentuate the relevance of hypoxia-responsive pathways in IBD and enhance understanding of immune cell dynamics across differing risk profiles. Subsequent investigations should seek to confirm these biomarkers in clinical contexts and investigate therapeutic strategies targeting hypoxia-related pathways for effective IBD management.", "claims": [{"id": "claim-method", "statement": "Differential gene examination between IBD (Ritchie et al., 2015) and control samples was executed employing the R package limma (Ritchie et al., 2015) (Version 3.54.2).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40771912", "locator": "sections[4] \"2.2 DEGs linked to IBD and hypoxia\" paragraph 2", "quote": "Differential gene examination between IBD (Ritchie et al., 2015) and control samples was executed employing the R package limma (Ritchie et al., 2015) (Version 3.54.2)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE48958, GSE75214, and GSE179285.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40771912", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: GEO database at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE48958, GSE75214, and GSE179285."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A diagnostic model integrating 13 hypoxia-related differentially expressed genes achieved an area under the curve exceeding 0.9 across various datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40771912", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A diagnostic model (DM) integrating 13 HRDEGs exhibited high accuracy, achieving an area under the curve (AUC) exceeding 0.9 across various datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A diagnostic model integrating 13 hypoxia-related differentially expressed genes achieved an area under the curve exceeding 0.9 across various datasets.", "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:40771912"], "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:GSE179285"], "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:GSE179285"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40771912", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2025.1612676", "sha256": "sha256:4e2d2501736810d017c6d4059daf593110129077fc5e9abd9581f826b1f40c3d", "bytes": 60695, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2025.1612676", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12325073", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE179285", "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=GSE179285", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE179285", "version": null, "note": "Publicly available datasets were analyzed in this study. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE48958", "GSE75214", "GSE179285"], "resolved_accessions": ["GSE48958", "GSE75214", "GSE179285"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: GEO database at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE48958, GSE75214, and GSE179285."], "basis": "The paper names GSE48958, GSE75214, GSE179285 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40771912", "data:geo:GSE179285"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE179285"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:58:35Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16762, "completion_tokens": 1261, "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:40771912", "type": "paper", "label": "pmid:40771912"}, {"id": "source:pmid:40771912", "type": "manuscript", "label": "PMID 40771912 full text"}, {"id": "data:geo:GSE179285", "type": "dataset", "label": "GEO GSE179285"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40771912", "type": "paper", "label": "pmid:40771912"}, {"id": "source:pmid:40771912", "type": "manuscript", "label": "PMID 40771912 full text"}, {"id": "data:geo:GSE179285", "type": "dataset", "label": "GEO GSE179285"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40771912", "type": "extraction", "used": ["source:pmid:40771912"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE179285", "type": "accession_resolution", "used": ["data:geo:GSE179285"], "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:40771912", "parent_hash": "sha256:f9f6744092f57872234875d4c0704f2555025672fb3c1fd4e45b908610229c7a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE179285 licence not read", "asset:data:geo:GSE179285 not downloaded", "asset:data:geo:GSE48958 licence not read", "asset:data:geo:GSE48958 not downloaded", "asset:data:geo:GSE75214 licence not read", "asset:data:geo:GSE75214 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Differential gene examination between IBD (Ritchie et al., 2015) and control samples was executed employing the R package limma (Ritchie et al., 2015) (Version 3.54.2)."], "order_basis": "analysis_only", "id": "assay:1"}]}