Comprehensive analysis of genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion injury.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41401161", "kind": "science-record", "revision": 4, "content_hash": "sha256:902f9af02912bc5b2338b436fcc21583f0fdf987e01fad2bb76110c9dd947c6e", "created_at": "2026-11-01T20:31:24Z", "updated_at": "2026-11-01T22:57:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion injury.", "doi": "10.1371/journal.pone.0338420", "pmid": "41401161", "authors": ["Shuang Bao", "YanBo Sun", "YiChen Hu", "XueFen Lei", "YuanPei Zhao", "WeiMing Li"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUND: Intestinal ischemia-reperfusion (II/R) injury is a severe clinical condition in which regulated cell death programs-including pyroptosis and necroptosis-have emerged as key drivers of tissue damage and inflammation. We sought to delineate cell-death-related molecular signatures and candidate therapeutic targets in II/R injury.\nMETHODS: We obtained transcriptome datasets from Gene Expression Omnibus (GEO) databases for mice (GSE96733, GSE232246) and humans (GSE37013). We cross-referenced genes associated with necroptosis and pyroptosis with differentially expressed genes to identify death-related features. Hub genes were identified through the topological structure of protein interaction networks and validated using an internal validation set, an independent validation set, WGCNA, and qRT-PCR. These genes were also associated with immune cell infiltration. Drug-gene interactions were predicted using DGIdb and verified through molecular docking.\nRESULTS: We identified 1,027 differentially expressed genes (DEGs) in the training set and derived 7 cell death-related differentially expressed genes (DCDEGs) by intersecting gene sets associated with necroptosis and pyroptosis. PPI-based prioritization identified four hub genes-Il1β, Ripk3, Sting1 (Tmem173), and Tnfaip3-suggesting cross-regulatory interactions between inflammation and cell death in ischemia-reperfusion pathology. These hub genes were validated using WGCNA analysis and an internal validation set. Immune infiltration analysis indicated significant correlations between hub genes and multiple immune compartments. A predictive model showed good discrimination in the discovery data, and 54 candidate drugs targeting the hub genes were retrieved. qRT-PCR confirmed dysregulation of three hub genes.\nCONCLUSION: Il1β, Ripk3, Sting1, and Tnaip3 were identified as hub genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion (II/R) injury. This study provides a reproducible framework and identifies testable targets for translational exploration.", "claims": [{"id": "claim-method", "statement": "This analysis was conducted using the “limma” package (version 3.64.1) in R software (version 4.5.0). DEGs were filtered using a threshold of |log₂FC| > 1 and an adjusted p-value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41401161", "locator": "sections[4] \"Differential expression analysis\" paragraph 2", "quote": "This analysis was conducted using the “limma” package (version 3.64.1) in R software (version 4.5.0). DEGs were filtered using a threshold of |log₂FC| > 1 and an adjusted p-value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We designated the GSE96733 dataset, based on the GPL23038 [Clariom_S_Mouse] platform, as the primary cohort and partitioned it into a training set (4 control groups and 4 II/R 3 h samples) and an internal validation set (4 control groups and 4 II/R 6 h samples).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41401161", "locator": "sections[3] \"Data sources and study design\" paragraph 2", "quote": "We designated the GSE96733 dataset, based on the GPL23038 [Clariom_S_Mouse] platform, as the primary cohort and partitioned it into a training set (4 control groups and 4 II/R 3 h samples) and an internal validation set (4 control groups and 4 II/R 6 h samples)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Il1β, Ripk3, Sting1, and Tnaip3 were identified as hub genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion (II/R) injury.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41401161", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Il1β, Ripk3, Sting1, and Tnaip3 were identified as hub genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion (II/R) injury."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Il1β, Ripk3, Sting1, and Tnaip3 were identified as hub genes associated with necroptosis and pyroptosis in intestinal ischemia-reperfusion (II/R) injury.", "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:41401161"], "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:GSE232246"], "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:GSE232246"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41401161", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0338420", "sha256": 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