Integrated Multi-omics Analysis of Hub Genes and miRNA Interactions in Hypertrophic Cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41450821", "kind": "science-record", "revision": 4, "content_hash": "sha256:a2bbaa5b1dac1cb870ea4d4f72ab0ccbc59c7e287dfe40fc393557e1cf08ec1d", "created_at": "2026-11-01T20:31:25Z", "updated_at": "2026-11-01T22:57:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Multi-omics Analysis of Hub Genes and miRNA Interactions in Hypertrophic Cardiomyopathy.", "doi": "10.2174/0113892029363785250311084956", "pmid": "41450821", "authors": ["Huanhuan Hu", "Ziheng Yu", "Kongjie Lu", "Hui Hu", "Lang Deng"], "journal": "Current genomics", "year": 2025, "abstract": "Background: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac disorder marked by the thickening of the heart muscle.\nMethods: HCM and normal control cell lines were cultured in DMEM with 12.5% FBS and 1% penicillin-streptomycin at 37°C and 5% CO2. Differentially expressed genes (DEGs) were identified from GSE32453, GSE53408, and GSE113439 datasets using the limma package in R. Hub genes were determined through protein-protein interaction (PPI) network and Cytoscape analysis and validated via Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment, miRNA predictions, drug prediction, and molecular docking analyses were conducted for functional enrichment and to explore hub gene-associated drugs.\nResults: To identify DEGs and hub genes implicated in HCM, we analyzed three Gene Expression Omnibus (GEO) datasets (GSE32453, GSE53404, and GSE1134439), extracting the top 1000 DEGs. Venn analysis revealed 21 common down-regulated genes. PPI analysis identified these six as key hub genes, including Iron Response Element Binding Protein 2 (IREB2), Protein Tyrosine Phosphatase, Non-Receptor Type 11 (PTPN11), IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), Phosphoglucomutase 2 (PGM2), DIS3 RNA Exonuclease 3' to 5' (DIS3), Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) in HCM patients. Gene enrichment analysis highlighted the involvement of these genes in cellular functions such as energy metabolism and growth factor signaling, suggesting their role in the disease's progression. Validation using an additional dataset (GSE36961) confirmed significant down-regulation of all hub genes in HCM samples, supported by Receiver Operating Characteristic (ROC) curve analysis that demonstrated their diagnostic potential. Furthermore, miRNA analysis identified six up-regulated miRNAs (miR-124, miR-29b, miR-330, miR-34a, miR-375, and miR-451) that likely contribute to the dysregulation of these hub genes. Drug prediction analysis identified various potential therapeutic compounds targeting these hub genes. Molecular docking revealed favorable binding affinities, supporting the therapeutic potential of these drugs in modulating hub gene activity.\nDiscussion: These findings demonstrate that HCM progression involves coordinated downregulation of hub genes and miRNA-mediated dysregulation of metabolic and signaling pathways. The integration of bioinformatics, validation assays, and drug docking suggests a strong translational potential for biomarker discovery and targeted therapy.\nConclusion: Our findings suggest that IREB2, PTPN11, IQGAP1, PGM2, DIS3, and GFPT1 hub genes and their associated regulatory pathways may serve as biomarkers and therapeutic targets for HCM, potentially improving diagnosis and treatment strategies.", "claims": [{"id": "claim-method", "statement": "The limma package in R software was utilized to identify DEGs between normal and HCM samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41450821", "locator": "sections[5] \"DEGs Identification\" paragraph 2", "quote": "The limma package in R software was utilized to identify DEGs between normal and HCM samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in this study, including GSE32453, GSE53408, GSE113439, and GSE36961, are publicly available in the Gene Expression Omnibus (GEO) database. These datasets can be accessed through the following link: https://www.ncbi.nlm.nih.gov/geo/. Data related to other molecular experiments can be provided by the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41450821", "locator": "sections[31] \"AVAILABILITY OF DATA AND MATERIALS\" paragraph 2", "quote": "The datasets analyzed in this study, including GSE32453, GSE53408, GSE113439, and GSE36961, are publicly available in the Gene Expression Omnibus (GEO) database. These datasets can be accessed through the following link: https://www.ncbi.nlm.nih.gov/geo/. Data related to other molecular experiments can be provided by the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Differentially expressed genes were identified from three GEO datasets using the limma package in R.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41450821", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified from GSE32453, GSE53408, and GSE113439 datasets using the limma package in R."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differentially expressed genes were identified from three GEO datasets using the limma package in R.", "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:41450821"], "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:GSE113439"], "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:GSE113439"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41450821", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2174/0113892029363785250311084956", "sha256": "sha256:9a85b05f7ca85b9cc5445e95d22286f0cbdb629dd0b9f0bd2e567f8e290359fa", "bytes": 41131, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2174/0113892029363785250311084956", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12728595", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE113439", "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=GSE113439", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE113439", "version": null, "note": "The datasets analyzed in this study, including GSE32453, GSE53408, GSE113439, and GSE36961, are publicly available in the Gene Expression Omnibus (GEO) database. These datasets can be accessed through the following link: https://www.ncbi.nlm.nih.gov/geo/. Data related to other molecular experiments can be provided by the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in this study, including GSE32453, GSE53408, GSE113439, and GSE36961, are publicly available in the Gene Expression Omnibus (GEO) database. These datasets can be accessed through the following link: https://www.ncbi.nlm.nih.gov/geo/. 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Methods: HCM and normal control cell lines were cultured in DMEM with 12.5% FBS and 1% penicillin-str", "hods: HCM and normal control cell lines were cultured in DMEM with 12.5% FBS and 1% penicillin-strept", "from Merck-Millipore, USA. These cells were cultured in DMEM supplemented with 12.5% FBS and 1% peni", "including AC16, iPSC-derived cardiomyocytes, HEK293, and HCM, along with three normal control ce"], "order_basis": "paper_text_order:209", "id": "assay:1"}, {"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": ["tion Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment,", "n Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment,", "were identified and designated as hub genes. RT-qPCR Analysis of Hub Genes on HCM Cell Lines RT-q", "qPCR Analysis of Hub Genes on HCM Cell Lines RT-qPCR was performed with the TaqMan™ Fast Advanced"], "order_basis": "paper_text_order:619", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["tive Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. Gene enrichment, miRNA predictions"], "order_basis": "paper_text_order:632", "id": "assay:3"}, {"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": ["The limma package in R software was utilized to identify DEGs between normal and HCM samples."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}