Identification and experimental validation of common genes associated with both pulmonary arterial hypertension and major depressive disorder.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41280439", "kind": "science-record", "revision": 4, "content_hash": "sha256:bb23e43d8382116fbe80c0f136e3deb655d34e6e96c63131a19987213688167a", "created_at": "2026-11-01T20:31:18Z", "updated_at": "2026-11-01T22:57:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and experimental validation of common genes associated with both pulmonary arterial hypertension and major depressive disorder.", "doi": "10.3389/fpsyt.2025.1670519", "pmid": "41280439", "authors": ["Yan Yan", "Mohammad Ismail Hajary Sagor", "Liang Chen", "Huakan Lin", "Gufeng Gao", "Guili Lian", "Liangdi Xie"], "journal": "Frontiers in psychiatry", "year": 2025, "abstract": "Background: Pulmonary arterial hypertension (PAH) and major depressive disorder (MDD) frequently co-occur, worsening morbidity and mortality. The shared genetic and molecular substrates of this comorbidity remain unclear. This study investigated common differentially expressed genes (DEGs), convergent pathways, and candidate hub genes linking PAH and MDD.\nMethods: Gene-expression datasets for PAH (GSE113439, GSE53408) and MDD (GSE44593, GSE54564) were obtained from GEO. After standardization, DEGs were identified with Limma, and intersected across diseases while retaining concordant expression trends. Functional enrichment was performed using Gene Ontology (GO). A protein-protein interaction (PPI) network was built to prioritize hub genes (CytoHubba), followed by feature selection with LASSO regression and additional machine-learning validation. Immune-cell infiltration was profiled to assess shared immunological alterations. An experimental rat model of PAH exhibiting anxiety- and depression-like behaviors was established, and hub-gene expression was validated by qPCR.\nResults: Forty-two common DEGs with consistent directions were identified. Network analysis and LASSO converged on six candidate hub genes; among these, CHD8, DDX42, and EIF3D were further supported by machine-learning validation. Immune-infiltration analysis indicated dysregulated immune landscapes in both PAH and MDD. In PAH rats, anxiety- and depression-like behaviors were observed, and qPCR confirmed altered expression of CHD8, DDX42, and EIF3D consistent with in-silico findings.\nConclusions: This integrative analysis highlights genetic and molecular links between PAH and MDD. CHD8, DDX42, and EIF3D emerge as candidate hub genes associated with the coexistence of these conditions, suggesting hypotheses for mechanistic follow-up and potential therapeutic targeting.", "claims": [{"id": "claim-method", "statement": "To identify the DEGs between cases and controls in the datasets, we used the “limma” package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41280439", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "To identify the DEGs between cases and controls in the datasets, we used the “limma” package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: The PAH datasets GSE113439 and GSE53408 as well as the MDD datasets GSE44593 and GSE54564 were retrieved from the Gene Expression Omnibus (GEO) database at https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41280439", "locator": "sections[34] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: The PAH datasets GSE113439 and GSE53408 as well as the MDD datasets GSE44593 and GSE54564 were retrieved from the Gene Expression Omnibus (GEO) database at https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The analysis identified 42 differentially expressed genes common to PAH and MDD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41280439", "locator": "sections[19] \"Identification of common DEGs between PAH and MDD\" paragraph 4", "quote": "The Venn diagram analysis revealed 42 DEGs common to both conditions (Figure 2E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The analysis identified 42 differentially expressed genes common to PAH and MDD.", "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:41280439"], "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:41280439", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fpsyt.2025.1670519", "sha256": "sha256:9fa46add600f69927b8ed2a71dbacf9d9da07b48add867c5a286da47b97246c8", "bytes": 77776, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fpsyt.2025.1670519", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12634556", "source": "europe_pmc_fulltext", "coverage": "whole_body", "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": "Publicly available datasets were analyzed in this study. 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An experimental rat model of PAH exhibiting anxiety- and depress", "mmune landscapes in both PAH and MDD. In PAH rats, anxiety- and depression-like behaviors were", "h the ARRIVE guidelines. Male Sprague–Dawley rats (8 weeks old) were obtained from Shanghai SL", "MCT; Sigma Aldrich, 30 mg/kg), while control rats received an equal volume of saline. Although"], "order_basis": "paper_text_order:1054", "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": ["ed, and hub-gene expression was validated by qPCR. Results: Forty-two common DEGs with consist", "depression-like behaviors were observed, and qPCR confirmed altered expression of CHD8, DDX42,", "nap-frozen in liquid nitrogen for subsequent qPCR analysis (25). 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