生物信息学
生物信息學
생물신식학
China Journal of Bioinformatics
2015年
3期
170-178
,共9页
韦云真%刘晓娟%王芳%苏建忠%张岩%刘洪波
韋雲真%劉曉娟%王芳%囌建忠%張巖%劉洪波
위운진%류효연%왕방%소건충%장암%류홍파
DNA甲基化%基因表达%转录调控%癌症
DNA甲基化%基因錶達%轉錄調控%癌癥
DNA갑기화%기인표체%전록조공%암증
DNA methylation%Gene expression%Transcriptional regulation%Cancer
DNA甲基化是一种重要的表观遗传学修饰,在基因的转录调控方面具有重要的作用. 异常的DNA甲基化可以导致癌症等复杂疾病发生,癌基因相关的DNA甲基化调控位点的识别对于解析癌症的发生发展机制及识别新的癌症标记具有重要意义. 本研究通过整合The Cancer Genome Atlas( TCGA)的泛癌症基因组的高通量甲基化谱和基因表达谱,识别癌基因相关的DNA甲基化调控位点. 对于每种癌症分批次计算CpG位点甲基化与相关基因表达之间的相关性,并筛选调控下游基因的CpG位点(包括强调控位点、弱调控位点和不调控位点) ,结果表明仅有一半的CpG位点对下游基因具有调控作用;对癌症间共享的调控位点的分析发现不同癌症间共享的调控位点不尽相同,表明癌症特异的甲基化调控位点的存在. 进一步地,对差异甲基化和差异表达基因的功能富集分析揭示了受甲基化调控的基因确实参与了癌症发生发展相关的功能. 本研究的结果是对当前甲基化调控位点集的重要补充,也是识别癌症新型分子标记特征的重要资源.
DNA甲基化是一種重要的錶觀遺傳學脩飾,在基因的轉錄調控方麵具有重要的作用. 異常的DNA甲基化可以導緻癌癥等複雜疾病髮生,癌基因相關的DNA甲基化調控位點的識彆對于解析癌癥的髮生髮展機製及識彆新的癌癥標記具有重要意義. 本研究通過整閤The Cancer Genome Atlas( TCGA)的汎癌癥基因組的高通量甲基化譜和基因錶達譜,識彆癌基因相關的DNA甲基化調控位點. 對于每種癌癥分批次計算CpG位點甲基化與相關基因錶達之間的相關性,併篩選調控下遊基因的CpG位點(包括彊調控位點、弱調控位點和不調控位點) ,結果錶明僅有一半的CpG位點對下遊基因具有調控作用;對癌癥間共享的調控位點的分析髮現不同癌癥間共享的調控位點不儘相同,錶明癌癥特異的甲基化調控位點的存在. 進一步地,對差異甲基化和差異錶達基因的功能富集分析揭示瞭受甲基化調控的基因確實參與瞭癌癥髮生髮展相關的功能. 本研究的結果是對噹前甲基化調控位點集的重要補充,也是識彆癌癥新型分子標記特徵的重要資源.
DNA갑기화시일충중요적표관유전학수식,재기인적전록조공방면구유중요적작용. 이상적DNA갑기화가이도치암증등복잡질병발생,암기인상관적DNA갑기화조공위점적식별대우해석암증적발생발전궤제급식별신적암증표기구유중요의의. 본연구통과정합The Cancer Genome Atlas( TCGA)적범암증기인조적고통량갑기화보화기인표체보,식별암기인상관적DNA갑기화조공위점. 대우매충암증분비차계산CpG위점갑기화여상관기인표체지간적상관성,병사선조공하유기인적CpG위점(포괄강조공위점、약조공위점화불조공위점) ,결과표명부유일반적CpG위점대하유기인구유조공작용;대암증간공향적조공위점적분석발현불동암증간공향적조공위점불진상동,표명암증특이적갑기화조공위점적존재. 진일보지,대차이갑기화화차이표체기인적공능부집분석게시료수갑기화조공적기인학실삼여료암증발생발전상관적공능. 본연구적결과시대당전갑기화조공위점집적중요보충,야시식별암증신형분자표기특정적중요자원.
DNA methylation is an important epigenetic modification,which plays an important role in the regulation of gene transcription.Abnormal DNA methylation may lead to cancer and disease,and identifying oncogene-related DNA methylation gene regulatory sites is important for the development of mechanisms to resolve the occurrence of cancer and identify new cancer markers. In this study,we integrate high-throughput DNA methylation profiling and gene expression profiling of pan-cancer genome in TCGA, then identify oncogene-related DNA methylation regulation sites.For each cancer,we calculate the correlation between methylation of CpG sites and gene expression, and filter the CpG sites, which regulate downstream genes( including strong regulatory sites, weak regulatory sites and not regulatory sites).The results show thatonly half of the CpG sites regulate the downstream genes.Analyzing of regulatory sites that is shared between cancers show that regulatory sites are not necessarily the same in different cancer,and the presence of cancer-specific methylation regulatory sites. Moreover,gene function enrichment analysis of differential DNA methylation and differentially expressed genes show that genes regulated by methylation are indeed involved in the development of cancer-related functions. The results of this study are an important supplementation to the current DNA methylation regulatory sites set, and an important resource to identify new molecular markers characteristics of cancer.