Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37985432", "kind": "science-record", "revision": 4, "content_hash": "sha256:12e2c57a91802aa8c47f51251ae65f29d251c383ef60f5d1112499e80f350af2", "created_at": "2026-11-01T19:02:54Z", "updated_at": "2026-11-01T22:53:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.", "doi": "10.1111/jcmm.18043", "pmid": "37985432", "authors": ["Yike Huang", "Dongqing Wang", "Wen Zhang", "Xue Yuan", "Ke Li", "Yuanyuan Zhang", "Mingqiang Zeng"], "journal": "Journal of cellular and molecular medicine", "year": 2024, "abstract": "This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.", "claims": [{"id": "claim-method", "statement": "The limma package (version: 3.40.2) in R software was utilized to analyse the differential expression of mRNAs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37985432", "locator": "sections[4] \"Data preprocessing and integration\" paragraph 2", "quote": "The limma package (version: 3.40.2) in R software was utilized to analyse the differential expression of mRNAs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37985432", "locator": "sections[27] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 66 cellular senescence-associated differentially expressed genes and eight hub genes associated with cellular senescence in diabetic foot ulcers.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37985432", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In total, 66 CS‐DEGs were obtained."}, {"asset": "source:pmid:37985432", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 66 cellular senescence-associated differentially expressed genes and eight hub genes associated with cellular senescence in diabetic foot ulcers.", "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:37985432"], "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:GSE80178"], "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:GSE80178"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37985432", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/jcmm.18043", "sha256": "sha256:23cc76a1b3a4b944593435bef165818240ccebf05b12b1451cc83eb79046d858", "bytes": 46520, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/jcmm.18043", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10805497", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE80178", "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=GSE80178", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE80178", "version": null, "note": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2114231", "GSM2114232", "GSM2114233", "GSM2114234", "GSM2114235", "GSM2114236", "GSM2114237", "GSM2114238", "GSM2114239", "GSM2114240", "GSM2114241", "GSM2114242"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "16686", "taxon": "Homo sapiens", "title": "Genomic Profiling of Diabetic Foot Ulcers Identifies miR-15b-5p as a Major Regulator that Leads to Suboptimal Inflammatory Response and Diminished DNA Repair Mechanisms", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE84971", "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=GSE84971", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE84971", "version": null, "note": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2254843", "GSM2254844", "GSM2254845", "GSM2254846", "GSM2254847", "GSM2254848"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "17537", "taxon": "Homo sapiens", "title": "Integrative Analysis of miRNA and mRNA Paired Expression Profiling of Primary Fibroblast Derived from Diabetic Foot Ulcers Reveals Multiple Impaired Cellular Functions", "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:GSE80178 not downloaded", "asset:data:geo:GSE80178 licence not read", "asset:data:geo:GSE84971 not downloaded", "asset:data:geo:GSE84971 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": "The limma package (version: 3.40.2) in R software was utilized to analyse the differential expression of mRNAs."}}, {"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": 0.8, "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": ["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": ["GSE80178", "GSE84971"], "resolved_accessions": ["GSE80178", "GSE84971"], "statements": ["The data analysed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article."], "basis": "The paper names GSE80178, GSE84971 in Gene Expression Omnibus (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:37985432", "data:geo:GSE80178"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE80178"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:59:34Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14456, "completion_tokens": 1847, "cached_tokens": 128}}, "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:37985432", "type": "paper", "label": "pmid:37985432"}, {"id": "source:pmid:37985432", "type": "manuscript", "label": "PMID 37985432 full text"}, {"id": "data:geo:GSE80178", "type": "dataset", "label": "GEO GSE80178"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37985432", "type": "paper", "label": "pmid:37985432"}, {"id": "source:pmid:37985432", "type": "manuscript", "label": "PMID 37985432 full text"}, {"id": "data:geo:GSE80178", "type": "dataset", "label": "GEO GSE80178"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37985432", "type": "extraction", "used": ["source:pmid:37985432"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE80178", "type": "accession_resolution", "used": ["data:geo:GSE80178"], "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:37985432", "parent_hash": "sha256:b0f85b39bb856d70eb00060c528ce704bcdb9dedc429e0db0f8898ac40cbec57", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE80178 licence not read", "asset:data:geo:GSE80178 not downloaded", "asset:data:geo:GSE84971 licence not read", "asset:data:geo:GSE84971 not downloaded", "execution.not_run", "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": ["The limma package (version: 3.40.2) in R software was utilized to analyse the differential expression of mRNAs."], "order_basis": "analysis_only", "id": "assay:1"}]}