Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39081806", "kind": "science-record", "revision": 2, "content_hash": "sha256:26e2473dcd158f90029d2775286ac047597cd22dd52a8d8af39a5558715fb82e", "created_at": "2026-11-01T20:29:09Z", "updated_at": "2026-11-01T21:33:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.", "doi": "10.3389/fgene.2024.1378340", "pmid": "39081806", "authors": ["Guina Liu", "Mingqi Tan", "Rui Liu", "Xuejin Lu", "Xiaoshuang Jiang", "Yunpeng Bai", "Zhigang Guo", "Fang Lu"], "journal": "Frontiers in genetics", "year": 2024, "abstract": "Purpose: Age-related macular degeneration (AMD) is a chronic and progressive macular degenerative disease that culminates in a gradual deterioration of central vision. Despite its prevalence, the key biomarkers for AMD have not yet been fully elucidated. In this study, we aimed to efficiently identify biomarkers crucial for diagnosing AMD. Methods: Three datasets pertaining to retinal pigment epithelium (RPE)/choroid tissues associated with AMD were selected from the GEO database. The GSE50195 dataset was utilized to conduct weighted gene co-expression network analysis (WGCNA) for identifying module genes linked to AMD. KEGG and GO enrichment analyses were subsequently conducted on these module genes. GSE29801 and GSE135092 datasets were subjected to differential expression analysis to pinpoint the DEGs intersecting with the module genes. Subsequently, wet AMD (wAMD) and dry AMD (dAMD) mouse models were developed, from which RPE/choroid tissues were harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA, we selected the \"antiquewhite4\" module (r = 0.91 and p = 7e-07), which contains a total of 325 genes. Through the intersection of module genes with DEGs, nine hub genes were identified. Pathways involved in complement and coagulation cascades, ECM-receptor interactions, unsaturated fatty acid biosynthesis, and fatty acid elongation play important roles in AMD. Notably, CDH18 demonstrated notable variance across all three datasets. Post validation using RT-qPCR experiments revealed a significant downregulation of CDH18 in both dAMD and wAMD. EGLN3 was expressed at low levels in wAMD. In dAMD, EYA2, LTB, and PODXL were significantly downregulated, whereas APOC1 was notably upregulated. Western blot confirmed that CDH18 was lowly expressed in dAMD and wAMD mouse models. Conclusion: CDH18 was identified as the key gene involved in the pathogenesis of AMD. An imbalance of the complement and coagulation cascades is a potential mechanism of AMD. This study provides a novel idea for diagnosing and treating AMD in the future.", "claims": [{"id": "claim-method", "statement": "Statistical analysis was performed with R 4.2.1 software (R Foundation for Statistical Computing, Vienna, Austria) and GraphPad Prism 9.0 software (GraphPad Software, Inc., La Jolla, CA) using an independent sample t-test when comparing the two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39081806", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Statistical analysis was performed with R 4.2.1 software (R Foundation for Statistical Computing, Vienna, Austria) and GraphPad Prism 9.0 software (GraphPad Software, Inc., La Jolla, CA) using an independent sample t-test when comparing the two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39081806", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CDH18 expression in both the dAMD and wAMD model groups was significantly lower than that in the control group.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "The detection of total mRNA from RPE/choroid tissues showed that CDH18 expression in both the dAMD and wAMD model groups was significantly lower than that in the control group (Figure 7A, p < 0.0001), which was consistent with the results from public datasets (Supplementary Figure S1)."}, "evidence": [{"asset": "source:pmid:39081806", "locator": "sections[22] \"Validation of the expression of hub genes\" paragraph 2", "quote": "The detection of total mRNA from RPE/choroid tissues showed that CDH18 expression in both the dAMD and wAMD model groups was significantly lower than that in the control group (Figure 7A, p < 0.0001), which was consistent with the results from public datasets (Supplementary Figure S1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CDH18 expression in both the dAMD and wAMD model groups was significantly lower than that in the control group.", "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:39081806"], "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:GSE135092"], "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:GSE135092"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39081806", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2024.1378340", "sha256": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE29801", "GSE135092", "GSE50195"], "resolved_accessions": ["GSE29801", "GSE135092", "GSE50195"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE29801, GSE135092, GSE50195 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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Conclusion: CDH18 was identified as", "iven free access to food and drinking water. Mice were housed in a pathogen-free room at constant t", "h light–dark cycle. Unless otherwise stated, mice were anesthetized with intraperitoneal ketamine ("], "order_basis": "paper_text_order:988", "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": ["were harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA,", "ss all three datasets. Post validation using RT-qPCR experiments revealed a significant downregul", "e harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA,", "all three datasets. Post validation using RT-qPCR experiments revealed a significant downregul"], "order_basis": "paper_text_order:1093", "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": 0.99, "evidence": ["ed to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA, we selected the \"", "ated, whereas APOC1 was notably upregulated. 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