Dual disease co-expression analysis reveals potential roles of estrogen-related genes in postmenopausal osteoporosis and Parkinson's disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39840278", "kind": "science-record", "revision": 3, "content_hash": "sha256:4fe195afadbe37d34094ff3c16ef172cc1fa342c5c1095633c0900cc2dba3ba9", "created_at": "2026-11-01T20:30:08Z", "updated_at": "2026-11-01T22:13:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Dual disease co-expression analysis reveals potential roles of estrogen-related genes in postmenopausal osteoporosis and Parkinson's disease.", "doi": "10.3389/fgene.2024.1518471", "pmid": "39840278", "authors": ["Dongdong Yu", "Jian Kang", "Chengguo Ju", "Qingyan Wang", "Ye Qiao", "Long Qiao", "Dongxiang Yang"], "journal": "Frontiers in genetics", "year": 2024, "abstract": "Introduction: The deficiency of estrogen correlates with a range of diseases, notably Postmenopausal osteoporosis (PMO) and Parkinson's disease (PD). There is a possibility that PMO and PD may share underlying molecular mechanisms that are pivotal in their development and progression. The objective of this study was to identify critical genes and potential mechanisms associated with PMO by examining co-expressed genes linked to PD.\nMethods: Initially, pertinent data concerning PMO and PD were obtained from the GWAS database, followed by conducting a Bayesian colocalization analysis. Subsequently, co-expressed genes from the PMO dataset (GSE35956) and the PD dataset (GSE20164) were identified and cross-referenced with estrogen-related genes (ERGs). Differentially expressed genes (DEGs) among PMO, PD, and ERGs were subjected to an array of bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses, in addition to protein-protein interaction (PPI) network analysis. The study also involved constructing TF-gene interactions, TF-microRNA coregulatory networks, interactions of hub genes with diseases, and validation through quantitative reverse transcription polymerase chain reaction (qRT-PCR).\nResults: The colocalization analysis uncovered shared genetic variants between PD and osteoporosis, with a posterior probability of colocalization (PPH4) measured at 0.967. Notably, rs3796661 was recognized as a shared genetic variant. A total of 11 genes were classified as DEGs across PMO, PD, and ERGs. Five principal KEGG pathways were identified, which include the p53 signaling pathway, TGF-beta signaling pathway, cell cycle, FoxO signaling pathway, and cellular senescence. Additionally, three hub genes-WT1, CCNB1, and SMAD7-were selected from the PPI network utilizing Cytoscape software. These three hub genes, which possess significant diagnostic value for PMO and PD, were further validated using GEO datasets. Interactions between transcription factors and genes, as well as between microRNAs and hub genes, were established. Ultimately, the expression trends of the identified hub genes were confirmed through qRT-PCR validation.\nConclusions: This study is anticipated to offer innovative approaches for identifying potential biomarkers and important therapeutic targets for both PMO and PD.", "claims": [{"id": "claim-method", "statement": "Bayesian colocalization analysis serves to evaluate the likelihood of one or more genetic variants causally influencing two correlated traits.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39840278", "locator": "sections[3] \"2.1 Bayesian colocalization analysis\" paragraph 3", "quote": "Bayesian colocalization analysis serves to evaluate the likelihood of one or more genetic variants causally influencing two correlated traits."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39840278", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bayesian colocalization identified a shared genetic variant between PD and OP, with PPH4 of 0.967 and rs3796661 identified as the common variant.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39840278", "locator": "sections[12] \"3.1 The result of bayesian colocalization analysis\" paragraph 2", "quote": "Colocalisation analysis indicated shared genetic variants between PD and OP, with a posterior probability of colocalisation (PPH4) of 0.967. In particular, rs3796661was identified as a common genetic variant."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Bayesian colocalization identified a shared genetic variant between PD and OP, with PPH4 of 0.967 and rs3796661 identified as the common variant.", "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:39840278"], "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:39840278", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2024.1518471", "sha256": "sha256:b320c5de5d9282164eba96ba07f52f8d7b5cbf0f6166203f49c66d296fb53b49", "bytes": 41357, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2024.1518471", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11747517", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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"}}, {"id": "method-3", "family": "genetic_association", "specific": "gwas", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["gwas_locus_scan"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "GWAS"}}, {"id": "method-4", "family": null, "specific": null, "label": "Bayesian colocalization analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Bayesian colocalization analysis serves to evaluate the likelihood of one or more genetic variants causally influencing two correlated traits."}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:39840278"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:45:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11620, "completion_tokens": 2115, "cached_tokens": 264}}, "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:39840278", "type": "paper", "label": "pmid:39840278"}, {"id": "source:pmid:39840278", "type": "manuscript", "label": "PMID 39840278 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39840278", "type": "paper", "label": "pmid:39840278"}, {"id": "source:pmid:39840278", "type": "manuscript", "label": "PMID 39840278 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39840278", "type": "extraction", "used": ["source:pmid:39840278"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:39840278", "parent_hash": "sha256:839507dbbd6b0251178bbf25a569571898fa8b7f39483809e0fa476e8767246a", "fork_of": null, "generation": 2}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "analysis_only", "id": "assay:1"}]}