Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer's Disease: An Integrated Epigenomic-Transcriptomic Analysis.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35310542", "kind": "science-record", "revision": 3, "content_hash": "sha256:c183b0af57fb9f27852e22a42cdb6391b1276be150672077feac5d3f230d945e", "created_at": "2026-11-01T18:14:06Z", "updated_at": "2026-11-01T21:27:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer's Disease: An Integrated Epigenomic-Transcriptomic Analysis.", "doi": "10.3389/fcell.2021.825729", "pmid": "35310542", "authors": ["Hui Song", "Jue Yang", "Wenfeng Yu"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Alzheimer's disease (AD) is characterized by the abnormal deposition of amyloid-β (Aβ) plaques and tau tangles in the brain and accompanied with cognitive impairment. However, the fundamental cause of this disease remains elusive. To elucidate the molecular processes related to AD, we carried out an integrated analysis utilizing gene expression microarrays (GSE36980 and GSE5281) and DNA methylation microarray (GSE66351) in temporal cortex of AD patients from the Gene Expression Omnibus (GEO) database. We totally discovered 409 aberrantly methylated and differentially expressed genes. These dysregulated genes were significantly enriched in biological processes including cell part morphogenesis, chemical synaptic transmission and regulation of Aβ formation. Through convergent functional genomic (CFG) analysis, expression cross-validation and clinicopathological correlation analysis, higher TGFBR3 level was observed in AD and positively correlated with Aβ accumulation. Meanwhile, the promoter methylation level of TGFBR3 was reduced in AD and negatively associated with Aβ level and advanced Braak stage. Mechanically, TGFBR3 might promote Aβ production by enhancing β- and γ-secretase activities. Further investigation revealed that TGFBR3 may exert its functions via Synaptic vesicle cycle, Calcium signaling pathway and MAPK signal pathway by regulating hub genes GNB1, GNG3, CDC5L, DYNC1H1 and FBXW7. Overall, our findings highlighted TGFBR3 as an AD risk gene and might be used as a diagnostic biomarker and therapeutic target for AD treatment.", "claims": [{"id": "claim-method", "statement": "GEO2R, an interactive web tool to perform comparisons on the microarray data, was utilized to identify differentially methylated genes and differentially expressed genes. For both differentially methylated genes and differentially expressed genes, p < 0.05 and |t| > 2 were used as the cutoff criteria.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35310542", "locator": "sections[4] \"Data Processing\" paragraph 2", "quote": "GEO2R, an interactive web tool to perform comparisons on the microarray data, was utilized to identify differentially methylated genes and differentially expressed genes. For both differentially methylated genes and differentially expressed genes, p < 0.05 and |t| > 2 were used as the cutoff criteria."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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For both differentially methylated genes and differentially expressed genes, p < 0.05 and |t| > 2 were used as the cutoff criteria."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (GEO2R), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35310542", "data:geo:GSE106241"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE106241"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:38:53Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15452, "completion_tokens": 2618, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35310542", "type": "paper", "label": "pmid:35310542"}, {"id": "source:pmid:35310542", "type": "manuscript", "label": "PMID 35310542 full text"}, {"id": "data:geo:GSE106241", "type": "dataset", "label": "GEO GSE106241"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35310542", "type": "paper", "label": "pmid:35310542"}, {"id": "source:pmid:35310542", "type": "manuscript", "label": "PMID 35310542 full text"}, {"id": "data:geo:GSE106241", "type": "dataset", "label": "GEO GSE106241"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35310542", "type": "extraction", "used": ["source:pmid:35310542"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE106241", "type": "accession_resolution", "used": ["data:geo:GSE106241"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35310542", "parent_hash": "sha256:7f9e8c6178f032532302f948e0e617a6d782e70f686386973a86e4c50ba45ad9", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE106241 licence not read", "asset:data:geo:GSE106241 not downloaded", "asset:data:geo:GSE36980 licence not read", "asset:data:geo:GSE36980 not downloaded", "asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE5281 not downloaded", "asset:data:geo:GSE66351 licence not read", "asset:data:geo:GSE66351 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"]}