SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions.
SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions.
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DOI：
10.1093/nar/gky691
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发表时间：
2018-11-16
影响因子：
14.9
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Zhou W;Triche TJ Jr;Laird PW;Shen H
我们报告了 Illumina HumanMmethylation450 和 MmethylationEPIC 阵列的 DNA 甲基化测量中的一类新的伪影。这些伪影反映了与目标 DNA 的杂交失败，通常是由于种系或体细胞缺失，并表现为错误报告的中间甲基化。这些伪影通常会在现有的预处理流程中幸存下来，伪装成表观遗传改变，并且可能会混淆全表观基因组关联研究和甲基化数量性状位点研究中的发现。我们在 R 包 SeSAMe 中实现了一个解决方案，带外 (OOB) 阵列杂交的 P 值 (pOOBAH)。我们的方法有效地掩盖了删除和超多态性区域，减少或消除了在体细胞删除的情况下经常删除的肿瘤抑制基因（例如CDKN2A和RB1）的表观遗传沉默的虚假报告。此外，我们的方法大大减少了技术变化，同时保留了 HM450 和 EPIC 平台测量内部和之间的生物变化。 SeSAMe 提供了一个轻量级、模块化的 DNA 甲基化数据分析套件，具有适合对数千个样本进行高效分析的高性能实施。
We report a new class of artifacts in DNA methylation measurements from Illumina HumanMethylation450 and MethylationEPIC arrays. These artifacts reflect failed hybridization to target DNA, often due to germline or somatic deletions and manifest as incorrectly reported intermediate methylation. The artifacts often survive existing preprocessing pipelines, masquerade as epigenetic alterations and can confound discoveries in epigenome-wide association studies and studies of methylation-quantitative trait loci. We implement a solution, P-value with out-of-band (OOB) array hybridization (pOOBAH), in the R package SeSAMe. Our method effectively masks deleted and hyperpolymorphic regions, reducing or eliminating spurious reports of epigenetic silencing at oft-deleted tumor suppressor genes such as CDKN2A and RB1 in cases with somatic deletions. Furthermore, our method substantially decreases technical variation whilst retaining biological variation, both within and across HM450 and EPIC platform measurements. SeSAMe provides a light-weight, modular DNA methylation data analysis suite, with a performant implementation suitable for efficient analysis of thousands of samples.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
9.5
作者：
Dedeurwaerder S;Defrance M;Bizet M;Calonne E;Bontempi G;Fuks F
通讯作者：
Fuks F
影响因子：
5.8
作者：
Kuan, Pei Fen;Wang, Sijian;Chu, Haitao
通讯作者：
Chu, Haitao