Integrated Bioinformatics-Based Identification of Potential Diagnostic Biomarkers Associated with Diabetic Foot Ulcer Development.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34513999", "kind": "science-record", "revision": 5, "content_hash": "sha256:0f9b2b5c517ba5081ada1aec30da1558a8b5326980be3883e43d6051e8601db2", "created_at": "2026-11-01T15:41:51Z", "updated_at": "2026-11-01T22:04:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Bioinformatics-Based Identification of Potential Diagnostic Biomarkers Associated with Diabetic Foot Ulcer Development.", "doi": "10.1155/2021/5445349", "pmid": "34513999", "authors": ["Long Qian", "Zhipeng Xia", "Ming Zhang", "Qiong Han", "Die Hu", "Sha Qi", "Danmou Xing", "Yan Chen", "Xin Zhao"], "journal": "Journal of diabetes research", "year": 2021, "abstract": "The present study was designed to detect possible biomarkers associated with diabetic foot ulcer (DFU) incidence in an effort to develop novel treatments for this condition. The GSE7014 and GSE29221 gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, after which differentially expressed genes (DEGs) were identified between DFU and healthy samples. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were performed to explore the functional roles of these genes. In total, 1192 DEGs were identified in the GSE7014 dataset (900 upregulated, 292 downregulated), while 1177 were identified in the GSE29221 dataset (257 upregulated, 919 downregulated). GO analyses revealed these DEGs to be significantly enriched in biological processes including sarcomere organization, muscle filament sliding, and the regulation of cardiac conduction, molecular functions including structural constituent of muscle, protein binding, and calcium ion binding, and cellular components including Z disc, myosin filament, and M band. These DEGs were also enriched in the adrenergic signaling in cardiomyoctes, dilated cardiomyopathy, and tight junction KEGG pathways. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with DFU development.", "claims": [{"id": "claim-method", "statement": "Genes that were differentially expressed in DFU samples were identified using the default settings of the GEO2R tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), with DEGs being those genes with a P < 0.05 and a ∣logFC | >1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34513999", "locator": "sections[4] \"2.2. DEG Identification\" paragraph 2", "quote": "Genes that were differentially expressed in DFU samples were identified using the default settings of the GEO2R tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/), with DEGs being those genes with a P < 0.05 and a ∣logFC | >1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34513999", "locator": "sections[13] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:34513999"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34513999", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/5445349", "sha256": "sha256:e6fa982ddc41f77b8ca4ffe3d844fd3aa88c22a042b9e37ce3595d486b69ac87", "bytes": 18011, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/5445349", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8426639", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:34513999:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3518380d1da3eb2df8366202583952230a871f0286761dee5e99e44722be02b8", "bytes": 2049, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#tab1", "version": null, "note": "Functional and pathway enrichment analyses for module genes. The top 3 terms were selected based upon p value rankings when >3 terms were enriched for a given category.", "structure": {"pmcid": "PMC8426639", "section_index": 9, "section_title": "3.2. Pathway Enrichment Analyses", "row_count": 21, "column_count": 5}, "table": {"label": "Table 1", "caption": "Functional and pathway enrichment analyses for module genes. The top 3 terms were selected based upon p value rankings when >3 terms were enriched for a given category.", "rows": [["A, biological processes"], ["Term", "Name", "Count", "P value", "Genes"], ["GO:0045214", "Sarcomere organization", "7", "1.3E-9", "FHOD3, MYH3, ACTN2, CASQ2, CAPN3, LDB3, CASQ1"], ["GO:0030049", "Muscle filament sliding", "4", "4.4E-4", "MYH3, ACTN2, MYL3, DMD"], ["GO:1903779", "Regulation of cardiac conduction", "4", "1.4E-3", "PLN, CASQ2, ATP2B2, CASQ1"], ["B, molecular functions"], ["Term", "Name", "Count", "P value", "Genes"], ["GO:0008307", "Structural constituent of muscle", "9", "4.8E-12", "MYOM1, PDLIM3, ACTN2, MYOT, MYL3, CAPN3, NEXN, DMD, MYOM2"], ["GO:0005515", "Protein binding", "50", "5.9E-4", "FHOD3, MYOM1, BTG1, LGALSL, LDB3, SAT1, N4BP2L2, HK2,MYOM2, MED14, JPH2, XPO4, RASSF5, CAPN3, KIF1B, CTSC,ACTN2, IGFBP3, MYH1, PPP1R3C, MYOT, PRR16, CASQ2, TKT, FKBP3, CAMK2B, USP54, MGST1, THBS1, GTF2E2, PDLIM3, UGP2, PLN,CMYA5, KCNN2, DMD, PPARGC1A, S100A11, MPZL2, LGI1, MYH7B,DTNA, FAM46C, AGL, DDIT4L, ATP2B2, PPP2R3A, EFNA1, PKIA, CUTC"], ["GO:0005509", "Calcium ion binding", "10", "2.2E-3", "ACTN2, MYL3, CASQ2, CAPN3, ATP2B2, PPP2R3A, CASQ1, THBS1, PLCD4, S100A11"], ["C, cellular component"], ["Term", "Name", "Count", "P value", "Genes"], ["GO:0030018", "Z disc", "11", "2.5E-11", "FHOD3, JPH2, PDLIM3, ACTN2, MYOT, CASQ2, CAPN3, NEXN, LDB3, KCNN2, DMD"], ["GO:0032982", "Myosin filament", "4", "2.9E-5", "MYH1, MYH7B, MYH3, MYOM2"], ["GO:0031430", "M band", "4", "9.1E-5", "MYOM1, CMYA5, MYOM2, MYOM3"], ["D, KEGG pathway"], ["Term", "Name", "Count", "P value", "Genes"], ["hsa04261", "Adrenergic signaling in cardiomyocytes", "5", "4.5E-3", "CAMK2B, PLN, MYL3, ATP2B2, PPP2R3A"], ["Hsa05414", "Dilated cardiomyopathy", "4", "8.0E-3", "PLN, SGCD, MYL3, DMD"], ["hsa04530", "Tight junction", "4", "8.8E-3", "MYH1, MYH7B, MYH3, ACTN2"], ["KEGG: Kyoto Encyclopedia of Genes and Genomes."]], "row_count": 21, "column_count": 5, "numeric_cells": 38, "header_rows": 2, "locator": "section[9]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:34513999:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c0a3ba225e7065d0ff338457f73301a11cb4a6f32cac5b94b77d23f842d31772", "bytes": 596, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#tab2", "version": null, "note": "Degree of top 10 genes in top module.", "structure": {"pmcid": "PMC8426639", "section_index": 10, "section_title": "3.3. 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