Integration analysis using bioinformatics and experimental validation on cellular signalling for sex differences of hypertrophic cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39535387", "kind": "science-record", "revision": 3, "content_hash": "sha256:bb987fcd0bc5bc31ec89a37737b4dfb86bd309833fc983715d12c1ddac4e07d0", "created_at": "2026-11-01T20:29:48Z", "updated_at": "2026-11-01T22:13:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integration analysis using bioinformatics and experimental validation on cellular signalling for sex differences of hypertrophic cardiomyopathy.", "doi": "10.1111/jcmm.70147", "pmid": "39535387", "authors": ["Hongyu Kuang", "Yanping Xu", "Guangliang Liu", "Yuhao Wu", "Zhiyan Gong", "Yuehui Yin"], "journal": "Journal of cellular and molecular medicine", "year": 2024, "abstract": "There is a paucity of research examining the molecular mechanisms underlying sex differences of clinical phenotypes and the prognosis in hypertrophic cardiomyopathy (HCM). The dataset GSE36961 was retrieved from Gene Expression Omnibus (GEO) database and comprehensive bioinformatics was employed to identify the core genes linked to sex differences in HCM patients. Additionally, gene set enrichment analysis (GSEA) was conducted to detect downstream signalling pathways. Furthermore, experimental validation was carried out using hearts from spontaneously hypertensive rats (SHRs). A comprehensive analysis revealed the identification of 208 differentially expressed genes (DEGs) in female patients with HCM with a notable downregulation of seven core genes. Notably, there were sex differences in the expression of ras dexamethasone-induced protein 1 (RASD1) and myosin 6 (MYH6) in HCM. Gene ontology (GO) analysis and GSEA demonstrated an enrichment of autophagy-related processes in disease progression in HCM females. Specifically, spearman's correlation analysis revealed a positive correlation between nicotinamide phosphoribosyl transferase (NAMPT) and RASD1 levels, particularly among female patients (R = 0.569, p < 0.001). Additionally, animal models confirmed that cardiac hypertrophy was more pronounced in SHR females compared to males. SHR females exhibited lower mRNA and protein expressions of RASD1 and NAMPT, which were associated with impaired autophagy. In this study, bioinformatics and validation using external data sets and animal models of left ventricular hypertrophy suggested that the RASD1/NAMPT axis is potentially a crucial mechanism underlying the elevated risk of cardiovascular disorders in HCM females, also pointing potentially prognostic biomarkers.", "claims": [{"id": "claim-method", "statement": "To investigate the impact of autophagy on sex differences in HCM, we employed Spearman's correlation analysis to identify correlations between the expressions of core genes and autophagy‐related genes obtained from the Human Autophagy Database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39535387", "locator": "sections[8] \"Spearman's correlation analysis\" paragraph 2", "quote": "To investigate the impact of autophagy on sex differences in HCM, we employed Spearman's correlation analysis to identify correlations between the expressions of core genes and autophagy‐related genes obtained from the Human Autophagy Database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The open‐access datasets are available through the following URL: https://www.ncbi.nlm.nih.gov database annotated by GPL10558 as a Series Matrix File.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39535387", "locator": "sections[28] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The open‐access datasets are available through the following URL: https://www.ncbi.nlm.nih.gov database annotated by GPL10558 as a Series Matrix File."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A comprehensive analysis revealed the identification of 208 differentially expressed genes (DEGs) in female patients with HCM with a notable downregulation of seven core genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39535387", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A comprehensive analysis revealed the identification of 208 differentially expressed genes (DEGs) in female patients with HCM with a notable downregulation of seven core genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A comprehensive analysis revealed the identification of 208 differentially expressed genes (DEGs) in female patients with HCM with a notable downregulation of seven core genes.", "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:39535387"], "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. 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A comprehensive analysis revealed th", "last century, the spontaneously hypertensive rats (SHRs) animal model has been considered as a", "pment of LVH in this study. Both SHR and WKY rats for this study were sourced from Vital River", "xperimental verification utilized WKY female rats (n = 6), WKY male rats (n = 6), SHR female r"], "order_basis": "paper_text_order:671", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["1 and NAMPT at protein levels (Figure 5E,G). Immunofluorescence staining also identified lower RASD1 (p = 0.", "Representative images of RASD1 expression by immunofluorescence staining of SHR hearts from females or males", "Representative images of NAMPT expression by immunofluorescence staining of SHR hearts from females or males"], "order_basis": "paper_text_order:7350", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ly hypertensive rats (SHR). (A, B) Real‐time qPCR analysis showed the mRNA expression of Anp (", "gher in females than males. (C, D) Real‐time qPCR analysis of the mRNA expression of Rasd1 (C)"], "order_basis": "paper_text_order:7826", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n SHR females than males. (E) Representative western blotting results of RASD1 and NAMPT at protein levels", "autophagic flux was examined in SHR hearts. Western blot analysis indicated increased P62 expression", "e P62 protein (A, B) expressions measured by Western blot in hypertrophic hearts from SHR females and", "e P62 protein (D, E) expressions measured by Western blot in hypertrophic hearts from SHR females and"], "order_basis": "paper_text_order:8114", "id": "assay:4"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To investigate the impact of autophagy on sex differences in HCM, we employed Spearman's correlation analysis to identify correlations between the expressions of core genes and autophagy‐related genes obtained from the Human Autophagy Database."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}