一种新的基于主成分的方法来识别Illumina Infinium MethylationEPIC BeadChip数据中的差异甲基化区域。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuanchao Zheng, Kathryn L Lunetta, Chunyu Liu, Alicia K Smith, Richard Sherva, Mark W Miller, Mark W Logue
{"title":"一种新的基于主成分的方法来识别Illumina Infinium MethylationEPIC BeadChip数据中的差异甲基化区域。","authors":"Yuanchao Zheng, Kathryn L Lunetta, Chunyu Liu, Alicia K Smith, Richard Sherva, Mark W Miller, Mark W Logue","doi":"10.1080/15592294.2023.2207959","DOIUrl":null,"url":null,"abstract":"<p><p>Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMR<sub>PC</sub>. Then, DMR<sub>PC</sub> and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMR<sub>PC</sub> identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMR<sub>PC</sub> was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMR<sub>PC</sub> identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMR<sub>PC</sub> was less clear. In conclusion, DMR<sub>PC</sub> is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2207959"},"PeriodicalIF":2.9000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193914/pdf/","citationCount":"0","resultStr":"{\"title\":\"A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.\",\"authors\":\"Yuanchao Zheng, Kathryn L Lunetta, Chunyu Liu, Alicia K Smith, Richard Sherva, Mark W Miller, Mark W Logue\",\"doi\":\"10.1080/15592294.2023.2207959\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMR<sub>PC</sub>. Then, DMR<sub>PC</sub> and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMR<sub>PC</sub> identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMR<sub>PC</sub> was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMR<sub>PC</sub> identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMR<sub>PC</sub> was less clear. In conclusion, DMR<sub>PC</sub> is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.</p>\",\"PeriodicalId\":11767,\"journal\":{\"name\":\"Epigenetics\",\"volume\":\"18 1\",\"pages\":\"2207959\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193914/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/15592294.2023.2207959\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2023.2207959","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

差异甲基化区域(DMRs)是在与表型相关的多个CpG位点上具有甲基化模式的基因组区域。在本研究中,我们提出了一种基于主成分(PC)的DMR分析方法,用于使用Illumina Infinium MethylationEPIC BeadChip(EPIC)阵列生成的数据。我们通过回归协变量上一个区域内CpG的M值来获得甲基化残差,提取残差的PC,然后组合PC之间的关联信息以获得区域显著性。在确定我们的方法的最终版本之前,在各种条件下估计了基于模拟的全基因组假阳性(GFP)率和真阳性率,我们将其命名为DMRPC。然后,DMRPC和另一种DMR方法coMethDMR用于对发现和复制队列中已知具有多个相关甲基化位点(年龄、性别和吸烟)的几种表型进行表观基因组范围的分析。在两种方法分析的区域中,DMRPC确定的全基因组显著年龄相关DMR比Co-MethDMR多50%。仅通过DMRPC鉴定的基因座的复制率高于仅通过Co-MethDMR鉴定的基因位点的复制率(DMRPC为90%,Co-Methdmr为76%)。此外,DMRPC在CpG相关性中等的区域中确定了可复制的关联,这些关联通常不会通过coMethDMR进行分析。对于性别和吸烟的分析,DMRPC的优势不太明显。总之,DMRPC是一种新的强大的DMR发现工具,它在CpG之间具有中等相关性的基因组区域中保留了力量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.

A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.

A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.

A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.

Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMRPC. Then, DMRPC and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMRPC identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMRPC was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMRPC identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMRPC was less clear. In conclusion, DMRPC is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信