A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies
文献类型：期刊论文
| 作者 | Teschendorff, Andrew E.1,2,3; Zheng, Shijie C.1; Breeze, Charles E.4; Beck, Stephan4; Zheng, Shijie C.5; , |
| 刊名 | BMC BIOINFORMATICS
 |
| 出版日期 | 2017 |
| 卷号 | 18期号:-页码:105 |
| 关键词 | Cellular heterogeneity DNA methylation EWAS |
| ISSN号 | 1471-2105 |
| DOI | 10.1186/s12859-017-1511-5 |
| 文献子类 | Article |
| 英文摘要 | Background: Intra-sample cellular heterogeneity presents numerous challenges to the identification of biomarkers in large Epigenome-Wide Association Studies (EWAS). While a number of reference-based deconvolution algorithms have emerged, their potential remains underexplored and a comparative evaluation of these algorithms beyond tissues such as blood is still lacking. Results: Here we present a novel framework for reference-based inference, which leverages cell-type specific DNAse Hypersensitive Site (DHS) information from the NIH Epigenomics Roadmap to construct an improved reference DNA methylation database. We show that this leads to a marginal but statistically significant improvement of cell-count estimates in whole blood as well as in mixtures involving epithelial cell-types. Using this framework we compare a widely used state-of-the-art reference-based algorithm (called constrained projection) to two non-constrained approaches including CIBERSORT and a method based on robust partial correlations. We conclude that the widely-used constrained projection technique may not always be optimal. Instead, we find that the method based on robust partial correlations is generally more robust across a range of different tissue types and for realistic noise levels. We call the combined algorithm which uses DHS data and robust partial correlations for inference, EpiDISH (Epigenetic Dissection of Intra-Sample Heterogeneity). Finally, we demonstrate the added value of EpiDISH in an EWAS of smoking. Conclusions: Estimating cell-type fractions and subsequent inference in EWAS may benefit from the use of nonconstrained reference-based cell-type deconvolution methods. |
| 学科主题 | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Mathematical & Computational Biology |
| WOS关键词 | DNA METHYLATION CHANGES ; HUMAN GENOME ; SYSTEMATIC ANNOTATION ; TUMOR PURITY ; CANCER ; PROFILES ; SUBSETS ; DECONVOLUTION ; VALIDATION ; MICROARRAY |
| 语种 | 英语 |
| WOS记录号 | WOS:000397490200001 |
| 出版者 | BIOMED CENTRAL LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1162]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China; 2.UCL, Dept Womens Canc, 74 Huntley St, London WC1E 6AU, England; 3.UCL, Stat Canc Genom, UCL Canc Inst, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England; 4.UCL, UCL Canc Inst, Med Genom, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England; 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Teschendorff, Andrew E.,Zheng, Shijie C.,Breeze, Charles E.,et al. A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies[J]. BMC BIOINFORMATICS,2017,18(-):105. |
| APA | Teschendorff, Andrew E.,Zheng, Shijie C.,Breeze, Charles E.,Beck, Stephan,Zheng, Shijie C.,&,.(2017).A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies.BMC BIOINFORMATICS,18(-),105. |
| MLA | Teschendorff, Andrew E.,et al."A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies".BMC BIOINFORMATICS 18.-(2017):105. |
入库方式： OAI收割
来源：上海营养与健康研究所
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