Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35280389", "kind": "science-record", "revision": 5, "content_hash": "sha256:39a3dc97a87df8621d620dce661b41f2003bab31722201fe407826eb6628faae", "created_at": "2026-11-01T18:14:03Z", "updated_at": "2026-11-01T22:48:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration.", "doi": "10.21037/atm-21-7043", "pmid": "35280389", "authors": ["Gaohua Liang", "Wenhao Ma", "Yanni Luo", "Jiayang Yin", "Lili Hao", "Jingxiang Zhong"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Age-related macular degeneration (AMD) is the leading cause of blindness for people over 50 years old worldwide. The purpose of this study was to identify differentially expressed and methylated genes (DEMGs) and construct a co-expression network for AMD.\nMethods: Microarray expression (GSE29801 dataset) and DNA methylation (GSE102952 dataset) profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were analyzed between AMD retina tissues and normal retina tissues. A protein-protein interaction (PPI) network was constructed and hub genes were screened, followed by functional enrichment analysis. Then, weighted gene co-expression network analysis (WGCNA) was conducted. The ARPE-19 cells were maintained in a hypoxic state to construct an AMD cellular model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation.\nResults: After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and up-regulated genes were identified for extramacular AMD. A total of 4 hub genes (LMNB2, EMD, HLA-A, and HLA-B) were screened for AMD in the extramacular retina. Furthermore, 13 hypermethylated and down-regulated genes and 31 hypomethylated and up-regulated genes were identified for macular AMD. Among them, 11 hub genes (HLA-A, HLA-B, HLA-DRB1, IFITM3, SAT1, MAOB, CHRDL1, FSTL1, HSPA1A, AR, and YAP1) were considered hub genes. The DEMGs were distinctly related with immune-related biological processes and pathways. A total of 16 co-expression modules were constructed, of which 2 significantly correlated with AMD. The genes in the 2 modules were involved in various crucial signaling pathways. The HIF1α and VEGF levels were significantly up-regulated in cell supernatant of hypoxia-induced ARPE-19 cells, indicating that the AMD cellular model was successfully established. Hub genes including CHRDL, FSTL1, and IFITM3 displayed significantly higher expression in hypoxia-induced ARPE-19 cells compared to normal cells. Greater up-regulation of CHRDL, FSTL1, and IFITM3 expression was found in hypoxia-induced ARPE-19 cells than in normal cells.\nConclusions: These findings offered several key DEMGs and pathways for AMD and constructed AMD-related co-expression modules, deepening understanding of the pathogenesis of AMD.", "claims": [{"id": "claim-method", "statement": "Differential expression and methylation analysis was presented using the limma package in R (https://www.rdocumentation.org/packages/limma/versions/3.28.14).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35280389", "locator": "sections[6] \"Differential expression and methylation analysis\" paragraph 2", "quote": "Differential expression and methylation analysis was presented using the limma package in R (https://www.rdocumentation.org/packages/limma/versions/3.28.14)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-21-7043/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35280389", "locator": "sections[31] \"(untitled)\" paragraph 1", "quote": "Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-21-7043/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and up-regulated genes were identified for extramacular AMD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35280389", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and up-regulated genes were identified for extramacular AMD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and up-regulated genes were identified for extramacular AMD.", "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:35280389"], "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:E-MTAB-7183"], "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:E-MTAB-7183"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35280389", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-21-7043", "sha256": 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Methods: Microarray expression (GSE29801 dataset) and DNA methyl"], "order_basis": "paper_text_order:377", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ar model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were perfo", "ic state to construct an AMD cellular model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) wer"], "order_basis": "paper_text_order:976", "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": ["orbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation. Results: Aft", "mmunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation. Res", "ent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation. Results: Aft"], "order_basis": "paper_text_order:1036", "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": ["Differential expression and methylation analysis was presented using the limma package in R (https://www.rdocumentation.org/packages/limma/versions/3.28.14)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}