PGK1: A Common Biomarker and Therapeutic Target Linking Sarcopenia and Osteoporosis Through Fibroblast-Mediated Pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41082466", "kind": "science-record", "revision": 4, "content_hash": "sha256:be4d4392b5180ec69f2879db196c1d1180dab345d5ee102e35d1da13f563a1d5", "created_at": "2026-11-01T20:31:08Z", "updated_at": "2026-11-01T22:57:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PGK1: A Common Biomarker and Therapeutic Target Linking Sarcopenia and Osteoporosis Through Fibroblast-Mediated Pathways.", "doi": "10.1049/syb2.70037", "pmid": "41082466", "authors": ["Kun Zhang", "Hailong Li", "Xinhong Chen", "Ping Tang", "Meng Wang", "Chunting Yang", "Rong Su", "Xiaqin Gao", "Fan Zhang", "Juan Han"], "journal": "IET systems biology", "year": 2025, "abstract": "Sarcopenia and osteoporosis share pathophysiological links, but their co-occurrence mechanisms remain unclear. This study aimed to identify molecular mediators of their co-development using bioinformatics. Datasets for sarcopenia (GSE56815) and osteoporosis (GSE9103) were retrieved from GEO. Differentially expressed genes (DEGs) were analysed via edgeR and limma. Gene ontology (GO), Kyoto encyclopaedia of genes and genomes (KEGG) and weighted gene co-expression network analysis (WGCNA) identified shared pathways and hub genes. Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. We validated hub genes in independent datasets (GSE13850, GSE8479) and assessed via ROC curves. Immune infiltration, single-cell analysis and drug prediction were performed. We identified 134 common DEGs (30 upregulated, 104 downregulated). WGCNA and PPI analysis revealed 14 hub genes (APOE, CDK2, PGK1, HRAS, RUNX2 etc.), all with ROC-AUC > 0.6. PGK1 was consistently downregulated in both diseases and linked to 21 miRNAs and six transcription factors (HSF1, TP53, JUN etc.). Single-cell analysis localised PGK1 predominantly in skeletal muscle fibroblasts. DrugBank identified lamivudine as a potential PGK1-targeting therapeutic. PGK1 emerged as a central downregulated gene in sarcopenia and osteoporosis, enriched in fibroblasts and modulated by lamivudine. These findings highlight PGK1 as a shared diagnostic and therapeutic target, offering insights into musculoskeletal crosstalk.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were analysed via edgeR and limma.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41082466", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Differentially expressed genes (DEGs) were analysed via edgeR and limma."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are available when requested by the readers from corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41082466", "locator": "sections[37] \"Data Availability Statement\" paragraph 2", "quote": "All data are available when requested by the readers from corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified PGK1 as a central downregulated shared gene and diagnostic and therapeutic target for sarcopenia and osteoporosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41082466", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "PGK1 emerged as a central downregulated gene in sarcopenia and osteoporosis, enriched in fibroblasts and modulated by lamivudine."}, {"asset": "source:pmid:41082466", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 134 common DEGs (30 upregulated, 104 downregulated)."}, {"asset": "source:pmid:41082466", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "WGCNA and PPI analysis revealed 14 hub genes (APOE, CDK2, PGK1, HRAS, RUNX2 etc.), all with ROC‐AUC > 0.6."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified PGK1 as a central downregulated shared gene and diagnostic and therapeutic target for sarcopenia and osteoporosis.", "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:41082466"], "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:GSE13850"], "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:GSE13850"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41082466", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1049/syb2.70037", "sha256": "sha256:b35b17d280d8b0e7aaab1c968da183d485337e48368a7ee762493182dffaa4f4", "bytes": 60589, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1049/syb2.70037", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12517354", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13850", "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=GSE13850", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13850", "version": null, "note": "All data are available when requested by the readers from corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available when requested by the readers from corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM179758", "GSM179759", "GSM179760", "GSM179761", "GSM179762", "GSM179763", "GSM179764", "GSM179765", "GSM179766", "GSM179767", "GSM179768", "GSM179769", "GSM179770", "GSM179771", "GSM179772", "GSM179773", "GSM179774", "GSM179775", "GSM179776", "GSM179777", "GSM348199", "GSM348200", "GSM348201", "GSM348202", "GSM348203", "GSM348204", "GSM348205", "GSM348206", "GSM348207", "GSM348208", "GSM348209", "GSM348210", "GSM348211", "GSM348212", "GSM348213", "GSM348214", "GSM348215", "GSM348216", "GSM348217", "GSM348218"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gene Expression of Circulating B Lymphocytes for Smoking-related Osteoporosis in Postmenopausal Females", "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:GSE56815", "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=GSE56815", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE56815", "version": null, "note": "All data are available when requested by the readers from corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available when requested by the readers from corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1369756", "GSM1369757", "GSM1369758", "GSM1369759", "GSM1369760", "GSM1369761", "GSM1369762", "GSM1369763", "GSM1369764", "GSM1369765", "GSM1369766", "GSM1369767", "GSM1369768", "GSM1369769", "GSM1369770", "GSM1369771", "GSM1369772", "GSM1369773", "GSM1369774", "GSM1369775", "GSM1369776", "GSM1369777", "GSM1369778", "GSM1369779", "GSM1369780", "GSM1369781", "GSM1369782", "GSM1369783", "GSM1369784", "GSM1369785", "GSM1369786", "GSM1369787", "GSM1369788", "GSM1369789", "GSM1369790", "GSM1369791", "GSM1369792", "GSM1369793", "GSM1369794", "GSM1369795", "GSM1369796", "GSM1369797", "GSM1369798", "GSM1369799", "GSM1369800", "GSM1369801", "GSM1369802", "GSM1369803", "GSM1369804", "GSM1369805", "GSM1369806", "GSM1369807", "GSM1369808", "GSM1369809", "GSM1369810", "GSM1369811", "GSM1369812", "GSM1369813", "GSM1369814", "GSM1369815", "GSM1369816", "GSM1369817", "GSM1369818", "GSM1369819", "GSM1369820", "GSM1369821", "GSM1369822", "GSM1369823", "GSM1369824", "GSM1369825", "GSM1369826", "GSM1369827", "GSM1369828", "GSM1369829", "GSM1369830", "GSM1369831", "GSM1369832", "GSM1369833", "GSM1369834", "GSM1369835"], "sample_count": 80, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gene expression study of blood monocytes in pre- and postmenopausal females with low or high bone mineral density (HG-U133A)", "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:GSE8479", "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=GSE8479", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE8479", "version": null, "note": "All data are available when requested by the readers from corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available when requested by the readers from corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM210289", "GSM210290", "GSM210291", "GSM210292", "GSM210293", "GSM210294", "GSM210295", "GSM210296", "GSM210297", "GSM210298", "GSM210299", "GSM210300", "GSM210301", "GSM210302", "GSM210303", "GSM210304", "GSM210305", "GSM210306", "GSM210307", "GSM210308", "GSM210309", "GSM210310", "GSM210311", "GSM210312", "GSM210313", "GSM210314", "GSM210315", "GSM210316", "GSM210317", "GSM210318", "GSM210319", "GSM210320", "GSM210321", "GSM210322", "GSM210323", "GSM210324", "GSM210325", "GSM210326", "GSM210327", "GSM210328", "GSM210329", "GSM210330", "GSM210331", "GSM210332", "GSM210333", "GSM210334", "GSM210335", "GSM210336", "GSM210337", "GSM210338", "GSM210339", "GSM210340", "GSM210341", "GSM210342", "GSM210343", "GSM210344", "GSM210345", "GSM210346", "GSM210347", "GSM210348", "GSM210349", "GSM210350", "GSM210351", "GSM210352", "GSM210353"], "sample_count": 65, "group_sizes": null, "group_sizes_basis": null, "platform": "2700", "taxon": "Homo sapiens", "title": "Resistance Exercise Reverses Aging in Human Skeletal Muscle", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE9103", "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=GSE9103", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE9103", "version": null, "note": "All data are available when requested by the readers from corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are available when requested by the readers from corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM230387", "GSM230388", "GSM230389", "GSM230390", "GSM230391", "GSM230392", "GSM230393", "GSM230394", "GSM230395", "GSM230396", "GSM230397", "GSM230398", "GSM230399", "GSM230400", "GSM230401", "GSM230402", "GSM230403", "GSM230404", "GSM230405", "GSM230406", "GSM230407", "GSM230408", "GSM230409", "GSM230410", "GSM230411", "GSM230412", "GSM230413", "GSM230414", "GSM230415", "GSM230416", "GSM230417", "GSM230418", "GSM230419", "GSM230420", "GSM230421", "GSM230422", "GSM230423", "GSM230424", "GSM230425", "GSM230426"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Skeletal Muscle Transcript Profiles in Trained or Sedentary Young and Old Subjects", "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:GSE13850 not downloaded", "asset:data:geo:GSE13850 licence not read", "asset:data:geo:GSE56815 not downloaded", "asset:data:geo:GSE56815 licence not read", "asset:data:geo:GSE8479 not downloaded", "asset:data:geo:GSE8479 licence not read", "asset:data:geo:GSE9103 not downloaded", "asset:data:geo:GSE9103 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "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": "Differentially expressed genes (DEGs) were analysed via edgeR and limma."}}, {"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": 0.7, "band": "medium", "quote": "limma"}}, {"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"}}], "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: edger."}, "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": ["GSE56815", "GSE9103", "GSE13850", "GSE8479"], "resolved_accessions": ["GSE56815", "GSE9103", "GSE13850", "GSE8479"], "statements": ["All data are available when requested by the readers from corresponding author."], "basis": "The paper names GSE56815, GSE9103, GSE13850, GSE8479 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:41082466", "data:geo:GSE13850"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13850"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:02:59Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16157, "completion_tokens": 1820, "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:41082466", "type": "paper", "label": "pmid:41082466"}, {"id": "source:pmid:41082466", "type": "manuscript", "label": "PMID 41082466 full text"}, {"id": "data:geo:GSE13850", "type": "dataset", "label": "GEO GSE13850"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41082466", "type": "paper", "label": "pmid:41082466"}, {"id": "source:pmid:41082466", "type": "manuscript", "label": "PMID 41082466 full text"}, {"id": "data:geo:GSE13850", "type": "dataset", "label": "GEO GSE13850"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41082466", "type": "extraction", "used": ["source:pmid:41082466"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13850", "type": "accession_resolution", "used": ["data:geo:GSE13850"], "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:41082466", "parent_hash": "sha256:8ef696c70adbe885f181784557dd3c30b445b80f2b7e4e6427acf5a0b8d3a43c", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE13850 licence not read", "asset:data:geo:GSE13850 not downloaded", "asset:data:geo:GSE56815 licence not read", "asset:data:geo:GSE56815 not downloaded", "asset:data:geo:GSE8479 licence not read", "asset:data:geo:GSE8479 not downloaded", "asset:data:geo:GSE9103 licence not read", "asset:data:geo:GSE9103 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": ["Differentially expressed genes (DEGs) were analysed via edgeR and limma."], "order_basis": "analysis_only", "id": "assay:1"}]}