Comprehensive bioinformatics analysis and experimental verification identify mitochondrial gene Dgat2 as a novel therapeutic biomarker for myocardial ischemia-reperfusion.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40510478", "kind": "science-record", "revision": 4, "content_hash": "sha256:486473b03bd81d8d99f39685576f2decaa57296f2eb257b32a3dcae47885d501", "created_at": "2026-11-01T20:30:37Z", "updated_at": "2026-11-01T22:56:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive bioinformatics analysis and experimental verification identify mitochondrial gene Dgat2 as a novel therapeutic biomarker for myocardial ischemia-reperfusion.", "doi": "10.3389/fendo.2025.1539646", "pmid": "40510478", "authors": ["Hong Li", "Yixin Zhou", "Wenya Xue", "Pan Yin", "Luyu Liu", "Shaobo Wu", "Yahao Zhao", "Qi An", "Yang Sun"], "journal": "Frontiers in endocrinology", "year": 2025, "abstract": "Background: Ischemic cardiomyopathy is a severe disease marked by high morbidity and mortality, often exacerbated by myocardial ischemia/reperfusion injury (MI/RI). Mitochondrial metabolism plays a critical role in MI/RI progression. This study aimed to identify potential new targets and biomarkers for mitochondria-related genes in MI/RI.\nMethods: MI/R microarray data (GSE160516) from the GEO database and a mitochondrial geneset were analyzed. Limma identified differentially expressed genes (DEGs), followed by GSEA, GO, and KEGG pathway enrichment. Mitochondria-related DEGs (MitoDEGs) were pinpointed. Protein-Protein Interaction (PPI) networks and machine learning identified key MitoDEGs. Regulatory networks were constructed using transcription factor (TF) predictions. Immune cell infiltration was assessed with ImmuCelAl, and correlations between MitoDEGs and immune cell levels were examined. Mouse myocardial ischemia-reperfusion models were established to validate pivotal MitoDEGs.\nResults: MitoDEGs were enriched in bio-oxidation, immune-inflammation, and oxidative stress pathways. Machine learning identified two hub genes: Dgat2 and Cybb. Dgat2 was significantly elevated in ischemia-reperfusion mouse models, confirmed by RT-PCR and Western blot. Functional enrichment indicated that Dgat2 may be involved in biological oxidation and lipid metabolism. TF prediction suggested PPARG as a regulator of Dgat2 expression. Immune infiltration analysis revealed significant correlations between Dgat2 and immune cells, including CD4_T_cells and NK cells, suggesting a role for immunity in MI/RI.\nConclusions: We found that Dgat2 could be exploited as a novel mitochondria-related gene target and biomarker in myocardial ischemia-reperfusion injury, which is of great clinical significance.", "claims": [{"id": "claim-method", "statement": "DEGs from the dataset were obtained with R package “limma” as implemented by Sangerbox (http://www.sangerbox.com/tool) (24), and all identified DEGs met p<0.05 and |log2 (Fold-change)|≥1.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40510478", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "DEGs from the dataset were obtained with R package “limma” as implemented by Sangerbox (http://www.sangerbox.com/tool) (24), and all identified DEGs met p<0.05 and |log2 (Fold-change)|≥1.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40510478", "locator": "sections[31] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:40510478"], "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:GSE160516"], "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:GSE160516"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40510478", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2025.1539646", "sha256": "sha256:20242011b5b9cc378bfe3e66ea1525636f72d6e2319e9a7185b6241471b30048", "bytes": 61503, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2025.1539646", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12159077", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE160516", "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=GSE160516", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE160516", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4874400", "GSM4874401", "GSM4874402", "GSM4874403", "GSM4874404", "GSM4874405", "GSM4874406", "GSM4874407", "GSM4874408", "GSM4874409", "GSM4874410", "GSM4874411", "GSM4874412", "GSM4874413", "GSM4874414", "GSM4874415"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "23038", "taxon": "Mus musculus", "title": "Expression data from mouse heart tissue ischemia/reperfusion (I/R) treated for 0,24,48,72 hours", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE160516 not downloaded", "asset:data:geo:GSE160516 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs from the dataset were obtained with R package “limma” as implemented by Sangerbox (http://www.sangerbox.com/tool) (24), and all identified DEGs met p<0.05 and |log2 (Fold-change)|≥1.5."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-Protein Interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE160516"], "resolved_accessions": ["GSE160516"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE160516 in NCBI GEO 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:40510478", "data:geo:GSE160516"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE160516"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:54:13Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17275, "completion_tokens": 1133, "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:40510478", "type": "paper", "label": "pmid:40510478"}, {"id": "source:pmid:40510478", "type": "manuscript", "label": "PMID 40510478 full text"}, {"id": "data:geo:GSE160516", "type": "dataset", "label": "GEO GSE160516"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40510478", "type": "paper", "label": "pmid:40510478"}, {"id": "source:pmid:40510478", "type": "manuscript", "label": "PMID 40510478 full text"}, {"id": "data:geo:GSE160516", "type": "dataset", "label": "GEO GSE160516"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40510478", "type": "extraction", "used": ["source:pmid:40510478"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE160516", "type": "accession_resolution", "used": ["data:geo:GSE160516"], "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:40510478", "parent_hash": "sha256:8332cc4365851da3a479554b2391588aecd9b6fa364cfcd316e084236e63d93f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE160516 licence not read", "asset:data:geo:GSE160516 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ondria-related genes in MI/RI. Methods: MI/R microarray data (GSE160516) from the GEO database and a", "ene expression profiling was performed using Affymetrix GeneChip mouse Genome 430 2.0 arrays (Affyme", "metrix GeneChip mouse Genome 430 2.0 arrays (Affymetrix, Inc.) on the GeneChip Mouse Genome 430 2.0"], "order_basis": "paper_text_order:482", "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": ["toDEGs and immune cell levels were examined. Mouse myocardial ischemia-reperfusion models were", "gnificantly elevated in ischemia-reperfusion mouse models, confirmed by RT-PCR and Western blot", "ons. Analysis of the immune microenvironment in mice treated with I/R for 24 h versus mice subjec", "ees of infiltration of multiple immune cells in mice, and that these immune cell infiltrations ma"], "order_basis": "paper_text_order:1033", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["fusion mouse models, confirmed by RT-PCR and Western blot. Functional enrichment indicated that Dgat2", "Dgat2 between the MI/R and Control groups by western blotting. The results showed that the protein express"], "order_basis": "paper_text_order:1381", "id": "assay:3"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["with qRT-PCR. The primer sequences used for qPCR are listed in Table 1 . As compared to the C"], "order_basis": "paper_text_order:3408", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["of mRNA (P<0.05) ( Figures 5I, J ). Further Immunohistochemical staining confirmed that myocardial Dgat2 exp"], "order_basis": "paper_text_order:3917", "id": "assay:5"}, {"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": ["DEGs from the dataset were obtained with R package “limma” as implemented by Sangerbox (http://www.sangerbox.com/tool) (24), and all identified DEGs met p<0.05 and |log2 (Fold-change)|≥1.5."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}