Network correlation analysis revealed potential new mechanisms for neural tube defects beyond folic acid.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29732722", "kind": "science-record", "revision": 5, "content_hash": "sha256:2a1824eb762f11b1498f301cb0ce1fd09e32c35ca8478ffcc98ad72be8d4d72b", "created_at": "2026-11-01T15:40:33Z", "updated_at": "2026-11-01T18:49:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Network correlation analysis revealed potential new mechanisms for neural tube defects beyond folic acid.", "doi": "10.1002/bdr2.1336", "pmid": "29732722", "authors": ["Xiaoya Gao", "Richard H Finnell", "Hongyan Wang", "Yufang Zheng"], "journal": "Birth defects research", "year": 2018, "abstract": "BACKGROUND: Neural tube defects (NTDs) are clinically significant congenital malformations which are known to be folic acid (FA) responsive, such that supplementation significantly reduces the prevalence of NTDs. Nonetheless, some individuals fail to respond to FA supplementation; hence NTDs remain a significant public health concern. The mechanisms that underlie the beneficial effects of FA supplementation remain poorly understood. Mouse models have been used extensively to study the mechanisms driving neural tube closure (NTC).\nMETHODS: Microarray data of GSE51285 was downloaded from the NCBI GEO database, which contains the RNA expression profiles of livers from five NTD mouse mutants (heterozygous females) and their corresponding wildtype (WT) controls. Those five NTD mutants have different responsiveness to FA supplementation. The differentially expressed genes (DEGs) between NTD heterozygous and WT mice, as well as the DEGs between FA-responsive and FA-resistant mutants were carefully examined. Weighted gene correlation network analysis (WGCNA) was performed in order to identify genes with high correlations to either FA responsiveness or NTDs, respectively.\nRESULTS: In total, we identified 18 genes related to the pathogenesis of NTDs, as well as 55 genes related to FA responsiveness. Eight more candidate genes (Abcc3, Gsr, Gclc, Mthfd1, Gart, Bche, Slc25a32, and Slc44a2) were identified by examining the DEGs of those genes involved in the extended folate metabolic pathway between FA-responsive and FA-resistant mutants.\nCONCLUSIONS: Those genes are involved in mitochondrial choline metabolism, de novo purine synthesis, and glutathione generation, suggesting that formate, choline, and manipulating antioxidant levels may be effective interventions in FA-resistant NTDs.", "claims": [{"id": "claim-target-result", "statement": "The study applied weighted gene correlation network analysis (WGCNA) to GSE51285 microarray data downloaded from the NCBI Gene Expression Omnibus database.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29732722", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Microarray data of GSE51285 was downloaded from the NCBI GEO database"}, {"asset": "source:pmid:29732722", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Weighted gene correlation network analysis (WGCNA) was performed in order to identify genes with high correlations to either FA responsiveness or NTDs, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study applied weighted gene correlation network analysis (WGCNA) to GSE51285 microarray data downloaded from the NCBI Gene Expression Omnibus database.", "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:29732722"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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