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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Frontiers Media S.A.
2020-10-01
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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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institution | Directory Open Access Journal |
issn | 1664-8021 |
language | English |
last_indexed | 2024-12-20T13:32:47Z |
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publisher | Frontiers Media S.A. |
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series | Frontiers in Genetics |
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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