Title: CpGFilter: model-based CpG probe filtering with replicates for epigenome-wide association studies.

Authors: Chen, Jun; Just, Allan C; Schwartz, Joel; Hou, Lifang; Jafari, Nadereh; Sun, Zhifu; Kocher, Jean-Pierre A; Baccarelli, Andrea; Lin, Xihong

Published In Bioinformatics, (2016 Feb 01)

Abstract: The development of the Infinium HumanMethylation450 BeadChip enables epigenome-wide association studies at a reduced cost. One observation of the 450K data is that many CpG sites the beadchip interrogates have very large measurement errors. Including these noisy CpGs will decrease the statistical power of detecting relevant associations due to multiple testing correction. We propose to use intra-class correlation coefficient (ICC), which characterizes the relative contribution of the biological variability to the total variability, to filter CpGs when technical replicates are available. We estimate the ICC based on a linear mixed effects model by pooling all the samples instead of using the technical replicates only. An ultra-fast algorithm has been developed to address the computational complexity and CpG filtering can be completed in minutes on a desktop computer for a 450K data set of over 1000 samples. Our method is very flexible and can accommodate any replicate design. Simulations and a real data application demonstrate that our whole-sample ICC method performs better than replicate-sample ICC or variance-based method.CpGFilter is implemented in R and publicly available under CRAN via the R package 'CpGFilter'.chen.jun2@mayo.edu or xlin@hsph.harvard.eduSupplementary data are available at Bioinformatics online.

PubMed ID: 26449931

MeSH Terms: No MeSH terms associated with this publication