STUDY OF NEURAL TUBE DEFECTS AND DNA METHYLATION MODIFICATIONS THROUGH THE PPI NETWORK

Bo Chi

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University.No.6 Shuangyong Road,

Qingxiu District, Nanning, 530021, Guangxi, China

Background: Failure of neural tube closure results in neural tube defects (NTDs), which may have severe neurological consequences or be fatal.

Methods: Differential analysis of NTDs and controls was performed separately for spinal and brain samples in GSE33111. Enrichment analysis for common genes of two groups of differentially expressed genes (DEGs). Differential methylation analysis was performed on NTDs and controls of spinal and brain samples from GSE69502, respectively. Enrichment analysis was performed on the intersection genes. Comparing the expression and methylation differences of genes obtained NTDs related genes subjected to methylation modification. PPI network analysis of common genes identified significant methylation marks.

Results: We found 2288 DEGs in the brain samples and 2267 DEGs in the spinal samples, for a total of 531 common genes. These genes were mainly enriched in type I interferon signaling pathway, and necroptosis. In addition, we found 2004 CPGs in brain samples and 3104 CPGs in spinal samples, for a total of 249 intersection genes. Methylation marks were significantly enriched in sensory organ morphogenesis, calcium ion transport into cytosol. Through the PPI network constructed on common genes, we identified the genes subjected to methylation modification in the network, which were considered as methylation marks (ANXA2, WIPF1 and KDM4B). Their methylation levels were reduced in NTDs compared to controls.

Conclusion: The interferon signaling pathway and calcium ion may be the molecular dysregulation mechanisms of NTDs. ANXA2, WIPF1 and KDM4B were identified as potential markers and target genes for NTDs.