Identification of potential hub genes associated with skin wound healing based on time course bioinformatic analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34193119", "kind": "science-record", "revision": 8, "content_hash": "sha256:df5b613472999428d0485acf49cc06ab7eda480eb13a64da597cab672da8f501", "created_at": "2026-11-01T15:41:40Z", "updated_at": "2026-11-01T22:46:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential hub genes associated with skin wound healing based on time course bioinformatic analyses.", "doi": "10.1186/s12893-021-01298-w", "pmid": "34193119", "authors": ["Hai-Jun Zhu", "Meng Fan", "Wei Gao"], "journal": "BMC surgery", "year": 2021, "abstract": "BACKGROUND: The skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer.\nMETHODS: Gene expression profiles of 37 biopsies collected from patients undergoing split-thickness skin grafts at five different time points were downloaded from two datasets (GSE28914 and GSE50425) in the Gene Expression Omnibus (GEO) database. Principal component analysis (PCA) was applied to classify samples into different phases. Subsequently, differentially expressed genes (DEGs) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment analyses were performed, and protein-protein interaction (PPI) networks created for each phase. Furthermore, based on the results of the PPI, hub genes in each phase were identified by molecular complex detection combined with the ClueGO algorithm.\nRESULTS: Using principal component analysis, the collected samples were divided into four phases, namely intact phase, acute wound phase, inflammatory and proliferation phase, and remodeling phase. Intact samples were used as control group. In the acute wound phase, a total of 1 upregulated and 100 downregulated DEGs were identified. Tyrosinase (TYR), tyrosinase Related Protein 1 (TYRP1) and dopachrome tautomerase (DCT) were considered as hub genes and enriched in tyrosine metabolism which dominate the process of melanogenesis. In the inflammatory and proliferation phase, a total of 85 upregulated and 164 downregulated DEGs were identified. CHEK1, CCNB1 and CDK1 were considered as hub genes and enriched in cell cycle and P53 signaling pathway. In the remodeling phase, a total of 121 upregulated and 49 downregulated DEGs were identified. COL4A1, COL4A2, and COL6A1 were considered as hub genes and enriched in protein digestion and absorption, and ECM-receptor interaction.\nCONCLUSION: This comprehensive bioinformatic re-analysis of GEO data provides new insights into the molecular pathogenesis of wound healing and the potential identification of therapeutic targets for the treatment of wounds.", "claims": [{"id": "claim-method", "statement": "Both the normalization of data and the screening of DEGs were performed using the linear models of microarray data (limma) package (http://bioconductor.org/packages/release/bioc/html/limma.html) within the R language environment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34193119", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "Both the normalization of data and the screening of DEGs were performed using the linear models of microarray data (limma) package (http://bioconductor.org/packages/release/bioc/html/limma.html) within the R language environment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34193119", "locator": "sections[22] \"notes\" paragraph 1", "quote": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34193119"], "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:GSE28914"], "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:GSE28914"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34193119", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12893-021-01298-w", "sha256": "sha256:6cdab81654595517b68a3211fa4040b3683d57a07ca13863517c6534fa0387ce", "bytes": 40150, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12893-021-01298-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8243612", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28914", "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=GSE28914", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28914", "version": null, "note": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM716451", "GSM716452", "GSM716453", "GSM716454", "GSM716455", "GSM716456", "GSM716457", "GSM716458", "GSM716459", "GSM716460", "GSM716461", "GSM716462", "GSM716463", "GSM716464", "GSM716465", "GSM716466", "GSM716467", "GSM716468", "GSM716469", "GSM716470", "GSM716471", "GSM716472", "GSM716473", "GSM716474", "GSM716475"], "sample_count": 25, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Human Skin Transcriptome during Epidermal Wound Healing", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE50425", "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=GSE50425", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50425", "version": null, "note": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data of GSE28914 and GSE50425 are available from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/). The datasets analysed during the current study are almost in the additional tables. If there are any other questions, please contact the corresponding author by email.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1219052", "GSM1219053", "GSM1219054", "GSM1219055", "GSM1219056", "GSM1219057", "GSM1219058", "GSM1219059", "GSM1219060", "GSM1219061", "GSM1219062", "GSM1219063"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Characterizing the wound healing response that drives human epidermal maturation on transcriptome level", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE28914 not downloaded", "asset:data:geo:GSE28914 licence not read", "asset:data:geo:GSE50425 not downloaded", "asset:data:geo:GSE50425 licence not read"]}, "analysis": {"state": "partial", "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": "Both the normalization of data and the screening of DEGs were performed using the linear models of microarray data (limma) package (http://bioconductor.org/packages/release/bioc/html/limma.html) within the R language environment."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "Principal component analysis"}}, {"id": "method-3", "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-4", "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": ["method.reader_differs_from_extractor"]}, "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. 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