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Analysing DNA Methylation Patterns Of Pan-cancer

Posted on:2018-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:S N YangFull Text:PDF
GTID:2334330518488034Subject:Engineering
Abstract/Summary:PDF Full Text Request
Cancer is also known as malignant neoplasm,which is a kind of disease caused by cell growth disorders and proliferation mechanism.The high incidence of cancer and the trend to young people cause a great threat to human health.Due to the cause of cancer is complicated and volatile,its pathogenesis is not clear now,so the research on the pathogenesis of cancer is very important.The occurrence of cancer is a complex process involving multiple genetic changes,including genetic and epigenetic mechanisms,and researchers have been working on these mechanisms for many years.Recent studies show that the disorder of gene expression system is the root cause of cancer,specifically refers to the heritable genes,including oncogenes,tumor suppressor genes and DNA repair related genes.Unlike genetics,epigenetics refers to that the sequence of DNA does not change,but the gene expression has genetically altered.It is worth noting that,this process is reversible.Therefore,epigenetics become a new target for cancer therapy.As an important component of epigenetic modification,DNA methylation has attracted much attention,and is known as "the fifth bases of genome".There have been many studies on DNA methylation patterns in recent years,but most researches have studied DNA methylation for single cancer,individual genes or smaller regions of the gene.Previous work is rarely based on whole genome-wide studies.In view of these problems,this paper analyses DNA methylation data from the perspective of Pan-Cancer at the whole genome level.The main innovative achievements of this paper are summarized as follows:1.From the perspective of Pan-Cancer,this study adopts clustering algorithm based on difference analysis to explore the DNA methylation patterns of various types of cancer,using six cancer cases provided in the Pan-cancer project.First,the methylation levels of the six cancer types were analyzed by SAM and the differential methylation sites were screened out.Then,the six group of methylation sites are intersected to explore the similarity and specificity of the methylation pattern on Pan-cancer.At last,the methylation level of methylation sites was clustered by AP,and nine methylated clusters were obtained and analyzed.2.By calculating the Pearson correlation coefficient between methylation and gene expression,the common regulatory sites of six cancers are identified.The results show that the relationship between methylation and gene expression is complex rather than a simple positive or negative correlation.There are 8 significant loci correlation,that is,cg26799474,cg12986110,cg11199713,cg09226786,cg10372302,cg09349723,cg18647268,cg1988381.3.Through the gene annotation and KEGG enrichment analysis,we concluded that the nine methylated clusters and the eight methylation regulation sites from this research have a good biological interpretation.First,the resulting gene corresponding to the methylation control site was expressed abnormally in a variety of cancers.Secondly,the enrichment analysis showed that the gene set in each methylation cluster is significant in the pathways of multiple cancers,and has a significant impact on the development of cancer.Our studies have also shown that common methylation patterns do exist indifferent types of cancers.Therefore,it is very important to explore the relationship between methylation patterns and cancer from the perspective of pan-cancer.All in all,we analyzed DNA methylation patterns of various cancers,and compared the similarity and specificity of methylation patterns in different tumor types.The work in this paper also reveal the important role of methylation in cancer occurrence and development,which provides theoretical basis for the clinical applications of methylation analysis.
Keywords/Search Tags:Pan-cancer, DNA methylation pattern, Differential methylation site, Cluster analysis, Gene expression
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