Identification and validation of mitochondrial-related genes in intestinal ischemia-reperfusion injury based on WGCNA and machine learning.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41234537", "kind": "science-record", "revision": 4, "content_hash": "sha256:2bbbdf87c3c5174fe38d11c987007af07ee571e464f1c2df60e0c62977e54f2b", "created_at": "2026-11-01T20:31:16Z", "updated_at": "2026-11-01T22:57:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of mitochondrial-related genes in intestinal ischemia-reperfusion injury based on WGCNA and machine learning.", "doi": "10.3389/fmolb.2025.1691749", "pmid": "41234537", "authors": ["YiChen Hu", "Jie Huang", "XiaoLi Min", "YuanPei Zhao", "JiaHui Wang", "HongYuan Liu", "KaiWen Shi", "WenLiang Li", "WeiMing Li"], "journal": "Frontiers in molecular biosciences", "year": 2025, "abstract": "Background: Severe ischemia-reperfusion (II/R) injury of the intestines is a leading cause of death and disability. According to earlier research, modulating mitochondrial function is the primary mechanism by which II/R injury is ameliorated. In order to further molecular diagnostics and discover possible treatment targets, it is essential to find biomarkers of mitochondria in II/R injury.\nMethods: The datasets GSE96733 and GSE37013, along with mitochondrial-related genes (MRGs), were obtained from the Gene Expression Omnibus (GEO) database and MitoCarta3.0, respectively. GSE96733 conducted differential expression gene (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) module screening. In order to find MRGs that were expressed differently, we got their intersection (DEMRGs) and gene enrichment analysis was carried out. The hub genes were screened using machine learning approaches, protein-protein interaction (PPI) network analysis, and Molecular Complex Detection (MCODE). A nomogram was developed for diagnostic evaluation. Furthermore, the relationship between hub gene expression profiles and immune infiltration landscapes was interrogated through immune cell infiltration analysis. The expression patterns of the hub genes were further validated in the II/R injury model through dataset validation and qRT-PCR assays. The procedure concluded in a gene-related hub network, DSigDB prediction of prospective therapeutic compounds, and molecular docking simulations of the drugs' binding affinity with important target proteins.\nResults: Hub genes have been found in five different DEMRGs: Pdk4, Yrdc, Bcl2l11, Bcl2a1d and Pmaip1. The nomogram model was beneficial for diagnosis. Dendritic cells (DC) and M2 macrophages are strongly linked to the 5 Hub genes, according to immune cell infiltration research. Afterwards, the regulatory network showed that hub genes and miRNAs had a complicated connection. Additionally, securinine and ABT-737 were anticipated to be possible therapeutic agents for II/R injury. The validation results for the four hub genes (Pdk4, Yrdc, Bcl2l11, and Pmaip1), obtained from both independent datasets and qRT-PCR, were consistent with the initial bioinformatics analysis.\nConclusion: Pdk4, Yrdc, Bcl2l11, and Pmaip1 have been identified as hub genes closely associated with mitochondrial function in eraly II/R injury, thereby providing a theoretical basis for the diagnosis and treatment of eraly II/R injury.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis between sham and II/R groups was conducted with the “limma” package in R, applying thresholds of |log2FC| ≥ 1 and an adjusted P-value <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41234537", "locator": "sections[3] \"2.1 Data used\" paragraph 2", "quote": "Differential expression analysis between sham and II/R groups was conducted with the “limma” package in R, applying thresholds of |log2FC| ≥ 1 and an adjusted P-value <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41234537", "locator": "sections[33] \"Data availability statement\" paragraph 2", "quote": "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."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 28 differentially expressed mitochondrial-related genes by intersecting mitochondrial-related genes, differentially expressed genes, and the blue and magenta WGCNA modules.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41234537", "locator": "sections[20] \"3.3 Identification of DEMRGs\" paragraph 2", "quote": "For the purpose of identifying 28 DEMRGs, we used the Xiantao Academic platform (https://www.xiantaozi.com/) to intersect MRGs, DEGs, and the blue and magenta modules from the WGCNA"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 28 differentially expressed mitochondrial-related genes by intersecting mitochondrial-related genes, differentially expressed genes, and the blue and magenta WGCNA modules.", "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:41234537"], "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:GSE37013"], "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:GSE37013"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41234537", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2025.1691749", "sha256": "sha256:88f25572197d9c69bd6a3c87a66cfc8a28ca03da96046abc02e10cc8bd30646c", "bytes": 73488, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2025.1691749", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12605187", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE37013", "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=GSE37013", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE37013", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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