MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips

Frontiers in Genetics
Zhenxing WangYadong Wang

Abstract

The Illumina Infinium HumanMethylation450 Beadchips have been widely utilized in epigenome-wide association studies (EWAS). However, the existing two types of probes (type I and type II), with the distribution of measurements of probes and dynamic range different, may bias downstream analyses. Here, we propose a method, MGMIN (M-values Gaussian-MIxture Normalization), to correct the probe designs based on M-values of DNA methylation. Our strategy includes fitting Gaussian mixture distributions to type I and type II probes separately, a transformation of M-values into quantiles and finally a dilation transformation based on M-values of DNA methylation to maintain the continuity of the data. Our method is validated on several public datasets on reducing probe design bias, reducing the technical variation and improving the ability to find biologically differential methylation signals. The results show that MGMIN achieves competitive performances compared to BMIQ which is a well-known normalization method on β-values of DNA methylation.

References

Oct 24, 2001·Bioinformatics·K Y YeungW L Ruzzo
Feb 28, 2002·Genome Biology·Wei PanChap T Le
Aug 16, 2011·Genomics·Marina BibikovaRichard Shen
Dec 1, 2011·Epigenomics·Sarah DedeurwaerderFrançois Fuks
Apr 7, 2017·Genome Medicine·Davide Degli EspostiZdenko Herceg

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Datasets Mentioned

BETA
GSE29290
GSM815138
GSE38268
GSM937824
GSE38266
GSE95036
GEO29290

Software Mentioned

SWAN
BMIQ
SQN
MGMIN
limma

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