非综合征型唇腭裂DNA甲基化谱的生物信息学分析

doi:10.19439/j.sjos.2019.01.011

上海口腔医学 ›› 2019, Vol. 28 ›› Issue (1): 57-62.doi: 10.19439/j.sjos.2019.01.011

非综合征型唇腭裂DNA甲基化谱的生物信息学分析

赵安达, 黄怡憬, 张海峰, 唐雯, 张美芳

上海交通大学医学院附属第九人民医院临床营养科,上海 200011

收稿日期:2018-10-19 修回日期:2019-01-15 出版日期:2019-02-25 发布日期:2019-04-12
通讯作者: 张美芳,E-mail：13671553198@126.com
作者简介:赵安达（1991-）,男,在读硕士研究生,E-mail：peterzhao7@163.com
基金资助:
上海市卫生局科研课题计划(20114103)

Study on DNA methylation profiles in non-syndromic cleft lip/palate based on bioinformatics

ZHAO An-da, HUANG Yi-jing, ZHANG Hai-feng, TANG Wen, ZHANG Mei-fang

Department of Clinical Nutrition, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Shanghai 200011, China

Received:2018-10-19 Revised:2019-01-15 Online:2019-02-25 Published:2019-04-12

摘要/Abstract

摘要： 目的:针对非综合征型唇腭裂（non-syndrome cleft lip/cleft, NSCL/P）DNA甲基化谱,采用生物信息学技术筛选NSCL/P异常甲基化位点和异常甲基化区域,探讨DNA甲基化与NSCL/P发病机制的关系。方法:从基因表达综合数据库（Gene Expression Omnibus, GEO）的数据集下载原始数据,纳入67例NSCL/P患者和59例无出生缺陷者的全血甲基化数据。数据分析包括①探针过滤、质控、归一化等数据清洗;②差异甲基化位点和差异甲基化区域等差异甲基化分析;③对差异甲基化区域所在的基因进行基因本体（Gene Ontology,GO）富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）信号通路富集分析,明确异常DNA甲基化对生物功能学的影响。采用R 3.4.3统计学软件进行数据清洗、筛选差异甲基化位点和差异甲基化区域,采用DAVID 6.8工具对差异甲基化区域进行GO和KEGG富集分析。结果:NSCL/P患者和正常对照者差异显著的甲基化位点共814个（校正P<0.001,|Δβ|>0.125）,其中NSCL/P组与对照组相比,高甲基化位点178个,低甲基化位点636个;差异显著的甲基化区域共386个（P<0.05）,其中高甲基化区域204个,低甲基化区域182个。GO富集分析显示,富集于7个生化过程相关的差异性甲基化基因共38个,富集于3个分子功能相关的差异性甲基化基因共163个,富集于3个细胞成分有关的差异性甲基化基因共114个（P<0.01）。KEGG通路分析显示,9个信号通路出现差异性甲基化基因富集,涉及59个基因（P<0.05）。结论:DNA甲基化异常可能是影响NSCL/P发生、发展的重要表观遗传学机制,为诊断标志物筛选和靶向干预提供了线索。

关键词: 非综合征型唇腭裂, DNA甲基化, 生物信息学

Abstract: PURPOSE: To study DNA methylation patterns of non-syndromic cleft lip/palate(NSCL/P) using bioinformatic methods, including methylated positions and regions. METHODS: Whole blood DNA methylation data of NSCL/P samples was download from Gene Expression Omnibus(GEO) database, including 67 NSCL/P cases and 59 controls without birth defects. Data analysis included ①data cleaning, such as probes filtering, quality control and normalization; ②differential methylation analysis, including methylated positions and regions; ③Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on differential methylated genes. R 3.4.3 software was used for data cleaning, differential methylated positions and regions analysis. DAVID6.8 tool was used for GO and KEGG analysis. RESULTS: 814 differential methylated positions were detected (adjusted P<0.001,|Δβ|>0.125）, of which 178 were hypermethylated in NSCL/P patients, and 636 were hypomethylated. In addition, 386 differential methylated regions were identified (P<0.05), of which 204 were hypermethylation regions and 182 were hypomethylation regions. GO analysis showed that 38 differential methylated genes were involved in 7 kinds of biological processes, 163 differential methylated genes were involved in 3 kinds of molecular functions, and 114 differential methylated genes were involved in 3 kinds of cellular components (P<0.01). KEGG analysis showed that 59 differential methylated genes were involved in 9 kinds of signal pathways. CONCLUSIONS: Abnormal DNA methylation patterns of NSCL/P might be an important epigenetic mechanism affecting the development of NSCL/P. This study might contribute to the identification of identification of biomarkers and targeted interventions of NSCL/P.

Key words: Non-syndromic cleft lip/palate, DNA methylation, Bioinformatics

中图分类号:

R782.2

赵安达, 黄怡憬, 张海峰, 唐雯, 张美芳. 非综合征型唇腭裂DNA甲基化谱的生物信息学分析[J]. 上海口腔医学, 2019, 28(1): 57-62.

ZHAO An-da, HUANG Yi-jing, ZHANG Hai-feng, TANG Wen, ZHANG Mei-fang. Study on DNA methylation profiles in non-syndromic cleft lip/palate based on bioinformatics[J]. Shanghai Journal of Stomatology, 2019, 28(1): 57-62.

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非综合征型唇腭裂DNA甲基化谱的生物信息学分析

Study on DNA methylation profiles in non-syndromic cleft lip/palate based on bioinformatics

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