4.5 Article

Accurate genome-scale percentage DNA methylation estimates from microarray data

期刊

BIOSTATISTICS
卷 12, 期 2, 页码 197-210

出版社

OXFORD UNIV PRESS
DOI: 10.1093/biostatistics/kxq055

关键词

DNA methylation; Epigenetics; Microarray

资金

  1. National Institutes of Health / National Cancer Institute [P50CA58236, 2P50HG003233-06]
  2. Department of Defense [PC073533]
  3. Maryland Stem Cell Research Fund [MSCRFE 0102-00]

向作者/读者索取更多资源

DNA methylation is a key regulator of gene function in a multitude of both normal and abnormal biological processes, but tools to elucidate its roles on a genome-wide scale are still in their infancy. Methylation sensitive restriction enzymes and microarrays provide a potential high-throughput, low-cost platform to allow methylation profiling. However, accurate absolute methylation estimates have been elusive due to systematic errors and unwanted variability. Previous microarray preprocessing procedures, mostly developed for expression arrays, fail to adequately normalize methylation-related data since they rely on key assumptions that are violated in the case of DNA methylation. We develop a normalization strategy tailored to DNA methylation data and an empirical Bayes percentage methylation estimator that together yield accurate absolute methylation estimates that can be compared across samples. We illustrate the method on data generated to detect methylation differences between tissues and between normal and tumor colon samples.

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