Significance Analysis and Statistical Dissection of Variably Methylated Regions

• Activity Number: 186
• Type: Invited
• Date/Time: Monday, August 1, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Andrew Jaffe*+
• Companies: The Johns Hopkins University
• Keywords: variably methylation regions (VMRs) ; bump finding ; multiple testing ; functional data analysis ; preprocessing

Abstract

It has recently been proposed that variation in DNA methylation at specific genomic locations may play an important role in the development of complex diseases such as cancer. Here we develop one- and two-group multiple testing procedures for identifying and quantifying regions of DNA methylation variability. Our method is the first genome-wide statistical significance calculation for increased or differential variability, as opposed to the traditional approach of testing for mean changes. We apply these procedures to genome-wide methylation data obtained from biological and technical replicates and provide the first statistical proof that variably methylated regions exist and are due to inter-individual variation. We also show that differentially variable regions in colon tumor and normal tissue show enrichment of gene regulating gene expression, cell morphogenesis, and development, supporting a biological role for DNA methylation variability in cancer.