Integrative Analysis Identifies 15 Genes As Key Regulators In The Brain Tissues Of Alzheimer Patients By Reanalyzing DNA Methylation And Proteomics Data

Alzheimer’s disease(AD)is one of the most common neurodegenerative diseases,but its pathological mechanism is still not clear,treatment and diagnosis methods are also limited.Epigenetic regulation is becoming increasingly important in AD.Joint analysis of two types of microarray datasets(gene expression and DNA methylation)to identify key methylation based regulatory genes will help us better understand the molecular biological mechanisms of AD.Objective:1.Joint analysis of proteomics and DNA methylation was conducted to understand its information characteristics;2.Identify the key regulatory genes involved in the intersection of methylation and proteomics;3.Explore the molecular biological mechanisms involved in key genes.Methods:From the Gene Expression Omnibus(GEO),we retrieved the proteomics dataset(GSE29676)and the DNA methylation profile dataset(GSE134379).First,we compared the AD group with the control group and selected the differentially expressed genes(DEGs)and differential methylation genes(DMGs)using the Limma R package and the Ch AMP methylation analysis package in R(v3.6.1).Then,we enriched the DEGs and DMGs to the significant biological functions using the cluster Profiler R package.Finally,a comprehensive analysis was conducted based on the intersections between DMGs and DEGs.Results:We identified 817 DEGs and 746 DMGs in patients with AD compared with controls.Cross-analysis revealed 15 genes that exhibited differential expression and methylation in AD: ABLIM1,ARHGEF7,MPG,RALGDS,TBPL1,WPF1,ZNF207,ARHGAP26,CANT1,CDK6,CTBP1,ESRRA,RNF13,SLC37A1,TBCD.After a comprehensive analysis,we found that CTBP,ESRRA,RALGDS,TBCD,WPF1 DNA methylation had a negative correlation with their expression.Conclusion:In this study,we identified 15 genes that present both DNA methylation and proteomics dataset.We highlighted the clinical implication of using these 15 genes as the key regulators or drug targets in AD.