Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34389038", "kind": "science-record", "revision": 7, "content_hash": "sha256:7a4a1ab0ece2509424bd2e5c4be7083554a0fda68e1e3ea923d975c6beac962f", "created_at": "2026-11-01T15:41:47Z", "updated_at": "2026-11-01T22:04:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles.", "doi": "10.1186/s13018-021-02658-1", "pmid": "34389038", "authors": ["Zhanyu Yang", "Delong Liu", "Rui Guan", "Xin Li", "Yiwei Wang", "Bin Sheng"], "journal": "Journal of orthopaedic surgery and research", "year": 2021, "abstract": "BACKGROUND: Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment.\nMETHODS: Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein-protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis.\nRESULTS: In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2.\nCONCLUSIONS: This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.", "claims": [{"id": "claim-method", "statement": "DEGs were screened by using classical t test and |Log2(FoldChange)| > 2 and adj. P < 0.05 was defined as a threshold and criteria for the identification of statistically significant DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34389038", "locator": "sections[4] \"Data processing and identification of DEGs\" paragraph 2", "quote": "DEGs were screened by using classical t test and |Log2(FoldChange)| > 2 and adj. P < 0.05 was defined as a threshold and criteria for the identification of statistically significant DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in published articles.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34389038", "locator": "sections[20] \"notes\" paragraph 1", "quote": "All data generated or analyzed during this study are included in published articles."}], "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:34389038"], "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:GSE94683"], "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:GSE94683"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34389038", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13018-021-02658-1", "sha256": "sha256:e2553122f6add10f604387ef7314f26bd83b1b8b5b55e05f6852e7a8286631c4", "bytes": 22328, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13018-021-02658-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8364104", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE94683", "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=GSE94683", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE94683", "version": null, "note": "All data generated or analyzed during this study are included in published articles.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in published articles.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2480834", "GSM2480835", "GSM2480836", "GSM2480837", "GSM2480838", "GSM2480839", "GSM2480840", "GSM2480841", "GSM2480842", "GSM2480843", "GSM2480844", "GSM2480845", "GSM2480846", "GSM2480847", "GSM2480848", "GSM2480849"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "10630", "taxon": "Homo sapiens", "title": "Transcriptome analysis of heterotopic ossification mesenchymal stromal cells", "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:GSE94683 not downloaded", "asset:data:geo:GSE94683 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 0.8, "band": "high", "quote": "Principal components analysis"}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "family": "regression_modelling", "specific": "ols", "label": "Regression modelling", "dsl_operations": ["ols_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "linear regression"}}, {"id": "method-4", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-5", "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-6", "family": null, "specific": null, "label": "classical t test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs were screened by using classical t test and |Log2(FoldChange)| > 2 and adj. P < 0.05 was defined as a threshold and criteria for the identification of statistically significant DEGs."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "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": ["GSE94683"], "resolved_accessions": ["GSE94683"], "statements": ["All data generated or analyzed during this study are included in published articles."], "basis": "The paper names GSE94683 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": ["pca_fit"], "assets": ["source:pmid:34389038", "data:geo:GSE94683"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE94683"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 16844, "completion_tokens": 1055, "cached_tokens": 5640}}, "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:34389038", "type": "paper", "label": "pmid:34389038"}, {"id": "source:pmid:34389038", "type": "manuscript", "label": "PMID 34389038 full text"}, {"id": "data:geo:GSE94683", "type": "dataset", "label": "GEO GSE94683"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34389038", "type": "paper", "label": "pmid:34389038"}, {"id": "source:pmid:34389038", "type": "manuscript", "label": "PMID 34389038 full text"}, {"id": "data:geo:GSE94683", "type": "dataset", "label": "GEO GSE94683"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34389038", "type": "extraction", "used": ["source:pmid:34389038"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE94683", "type": "accession_resolution", "used": ["data:geo:GSE94683"], "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:34389038", "parent_hash": "sha256:e1e50ce3744d10c80f65464d4095559737fe47d93a9f9e593dc0e900da11a015", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE94683 licence not read", "asset:data:geo:GSE94683 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Principal components analysis"], "order_basis": "analysis_only", "id": "assay:1"}]}