Integrative bioinformatics approach for identifying key genes and potential therapeutic targets in the concurrent manifestation of hypertrophic cardiomyopathy and pulmonary hypertension.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38883633", "kind": "science-record", "revision": 4, "content_hash": "sha256:4cae74950faa8a7718f9264f16f8ae6754a72554e6276bd1a25347dd59dc3b4c", "created_at": "2026-11-01T20:28:57Z", "updated_at": "2026-11-01T22:54:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative bioinformatics approach for identifying key genes and potential therapeutic targets in the concurrent manifestation of hypertrophic cardiomyopathy and pulmonary hypertension.", "doi": "10.21037/jtd-23-1822", "pmid": "38883633", "authors": ["Xi Zheng", "Chenyang Zhang", "Tao Yang", "Zhanyang Luo", "Junyi Xia", "Weibin Tian", "Juan Shao", "Hu Zhang", "Jingru Gong", "Xuhui Bao"], "journal": "Journal of thoracic disease", "year": 2024, "abstract": "Background: Hypertrophic cardiomyopathy (HCM), identified as a primary cause of sudden cardiac death (SCD), intertwines with pulmonary hypertension (PH) to amplify cardiovascular morbidity. This complex synergy poses significant therapeutic challenges due to the absence of drugs specifically targeting their concurrent manifestation. This study seeks to unravel the molecular intricacies linking HCM and PH, aiming to lay the groundwork for targeted therapeutic interventions.\nMethods: Through the analysis of gene expression profiles from datasets GSE36961 (HCM) and GSE113439 (PH) within the public data repository of Gene Expression Omnibus (GEO), this research systematically identified differentially expressed genes (DEGs), conducted extensive functional annotations, and constructed detailed protein-protein interaction (PPI) networks to uncover crucial hub genes. Further, co-expression analyses, alongside drug prediction and molecular docking simulations, were employed to pinpoint potential therapeutic agents that could ameliorate the combined pathology of HCM and PH.\nResults: Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes. Validation across three additional datasets (GSE35229, GSE32453, and GSE53408) from GEO accentuated secreted phosphoprotein 1 (SPP1) as a key gene of interest. Remarkably, the study identified tacrolimus, ponatinib, bosutinib, dasatinib, doxorubicin, and zanubrutinib as promising drugs for addressing the dual challenge of HCM and PH.\nConclusions: The findings of this investigation shed light on the genetic underpinnings of HCM and PH's simultaneous occurrence, emphasizing the central role of SPP1 in their pathogenesis. The identification of six candidate drugs offers a hopeful vista for future therapeutic strategies targeting this complex cardiovascular interplay, marking a significant stride towards mitigating the compounded morbidity of HCM and PH. Future mechanistic and clinical studies are warranted for the investigation of this potential target and therapeutics.", "claims": [{"id": "claim-method", "statement": "GEO2R based on R language “limma” package, is a function recently updated by the GEO. It was used to screen DEGs by calculating and visualizing the differential expression multiple [settings: P<0.05, absolute fold change (FC) ≥1.5].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "GEO2R based on R language “limma” package, is a function recently updated by the GEO. It was used to screen DEGs by calculating and visualizing the differential expression multiple [settings: P<0.05, absolute fold change (FC) ≥1.5]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[4] \"Data acquisition\" paragraph 2", "quote": "GSE36961 contained 106 HCM and 39 non-HCM samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub 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:38883633"], "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:38883633", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/jtd-23-1822", "sha256": 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