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

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,...

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Main Authors: Zhenxing Wang, Yongzhuang Liu, Yadong Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2020.538492/full
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author Zhenxing Wang
Yongzhuang Liu
Yadong Wang
author_facet Zhenxing Wang
Yongzhuang Liu
Yadong Wang
author_sort Zhenxing Wang
collection DOAJ
description 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.
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spelling doaj.art-b11ba6464f9742cb838f3d3e750b07662022-12-21T19:39:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-10-011110.3389/fgene.2020.538492538492MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChipsZhenxing WangYongzhuang LiuYadong WangThe 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.https://www.frontiersin.org/articles/10.3389/fgene.2020.538492/fullDNA methylationdesign biasnormalizationM-valueGaussian mixture modelIllumina Infinium 450K
spellingShingle Zhenxing Wang
Yongzhuang Liu
Yadong Wang
MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
Frontiers in Genetics
DNA methylation
design bias
normalization
M-value
Gaussian mixture model
Illumina Infinium 450K
title MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
title_full MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
title_fullStr MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
title_full_unstemmed MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
title_short MGMIN: A Normalization Method for Correcting Probe Design Bias in Illumina Infinium HumanMethylation450 BeadChips
title_sort mgmin a normalization method for correcting probe design bias in illumina infinium humanmethylation450 beadchips
topic DNA methylation
design bias
normalization
M-value
Gaussian mixture model
Illumina Infinium 450K
url https://www.frontiersin.org/articles/10.3389/fgene.2020.538492/full
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AT yadongwang mgminanormalizationmethodforcorrectingprobedesignbiasinilluminainfiniumhumanmethylation450beadchips