Identification The Characteristics Of Age-related Differentially Methylated And Differentially Expressed Genes

DNA methylation is an important epigenetic modification that plays an important regulatory role in embryonic development,X chromosome inactivation,genomic imprinting and chromosome structure.DNA methylation is an important mechanism of gene silencing and regulation of gene expression.So far,the complex relationship between DNA methylation and gene expression is not yet clear.Recently scholars of related fields have carried out a great deal of research on age-related DNA methylation,however,the characteristic of age-related differentially methylated genes is unclear.In this thesis,we studied the relationship between differentially methylated regions and gene expression and identified their characteristics.The main research work and achievements are as follows:In this thesis,based on the region analysis,the matched methylomic and transcriptomic data with the big age-gap of sample were used to identified age-related differentially methylated regions(DMR),differentially expressed and simultaneously differentially methylated genes.We utilized genomic annotation data to analyzed the characteristic of differentially methylated regions,the results showed that for the same gene the variation patterns of various DMRs are highly consistent in its genomic location(either hyper-methylation or hypo-methylation).Furthermore,we analyzed the characteristic of the distribution of differentially methylated regions,the results showed that the hyper-and hypo-methylation regions are distributed non-uniformly,which tend to CGI promoter gene and non CGI promoter gene,respectively.In addition,our study also found that Gene Body which contains the majority of differentially methylated regions(including differentially and non-differentially expressed genes)is an important regulatory region of DNA methylation.We utilized expression data to analyzed the relationship between DNA methylation and gene expression in this thesis.For the relationship between the DMR and its corresponding gene expression(including non-differential expression or up-regulation or down-regulation),the result showed three types of relevance(i.e.positive,negative and no correlation)exist at the same time,which is a strong evidence demonstrating the complex relationship between methylation and geneexpression.Furthermore,there still has a tendency: the majority of DMR of non-differential expression has a positive correlation and that of differential expression has negative correlation.For the characteristics of positive correlated and negative correlated genes of differential methylation and differential expression,we analyzed them from two aspects.First of all,a human protein-protein interaction network is built by integrating the interacted data from multiple databases.Several centrality methods are adopted to construct the classification characteristics.And we used them to classify the two categories genes.We found the information of protein interaction networks is helpful to improve the performance of classifying the positive correlated and negative correlated genes of differential methylation and differential expression.In addition,We carried out the GO enrichment analysis on the positive correlated and negative correlated genes of differential methylation and differential expression,and the analysis result showed that there is a great difference between the enriched terms of these two categories of genes.The above results indicated that the two kinds of genes could possibly relate to different function modules of protein interaction and be associated with different transcription regulation patterns.