Detection of epigenetic field defects using a weighted epigenetic distance-based method

Ya Wang, Min Qian, Peifeng Ruan, Andrew E. Teschendorff, Shuang Wang

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Identifying epigenetic field defects, notably early DNA methylation alterations, is important for early cancer detection. Research has suggested these early methylation alterations are infrequent across samples and identifiable as outlier samples. Here we developed a weighted epigenetic distance-based method characterizing (dis)similarity in methylation measures at multiple CpGs in a gene or a genetic region between pairwise samples, with weights to up-weight signal CpGs and down-weight noise CpGs. Using distance-based approaches, weak signals that might be filtered out in a CpG site-level analysis could be accumulated and therefore boost the overall study power. In constructing epigenetic distances, we considered both differential methylation (DM) and differential variability (DV) signals. We demonstrated the superior performance of the proposed weighted epigenetic distance-based method over nonweighted versions and site-level EWAS (epigenome-wide association studies) methods in simulation studies. Application to breast cancer methylation data from Gene Expression Omnibus (GEO) comparing normal-adjacent tissue to tumor of breast cancer patients and normal tissue of independent age-matched cancer-free women identified novel epigenetic field defects that were missed by EWAS methods, when majority were previously reported to be associated with breast cancer and were confirmed the progression to breast cancer. We further replicated some of the identified epigenetic field defects.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages109-131
Number of pages23
DOIs
StatePublished - 2020
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume2117
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • DNA methylation
  • Epigenetic field defects
  • Weighted distance-based method

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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