ENmix: a novel background correction method for Illumina HumanMethylation450 BeadChip

Nucleic Acids Research
Zongli XuJack A Taylor

Abstract

The Illumina HumanMethylation450 BeadChip is increasingly utilized in epigenome-wide association studies, however, this array-based measurement of DNA methylation is subject to measurement variation. Appropriate data preprocessing to remove background noise is important for detecting the small changes that may be associated with disease. We developed a novel background correction method, ENmix, that uses a mixture of exponential and truncated normal distributions to flexibly model signal intensity and uses a truncated normal distribution to model background noise. Depending on data availability, we employ three approaches to estimate background normal distribution parameters using (i) internal chip negative controls, (ii) out-of-band Infinium I probe intensities or (iii) combined methylated and unmethylated intensities. We evaluate ENmix against other available methods for both reproducibility among duplicate samples and accuracy of methylation measurement among laboratory control samples. ENmix out-performed other background correction methods for both these measures and substantially reduced the probe-design type bias between Infinium I and II probes. In reanalysis of existing EWAS data we show that ENmix can identify additio...Continue Reading

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Citations

Mar 29, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Kelly M BakulskiM Daniele Fallin
Jun 22, 2016·Briefings in Functional Genomics·Dao-Peng ChenCathy S J Fann
Jul 28, 2016·Current Opinion in Structural Biology·Annabel Ha ParretRob Meijers
Mar 22, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Yuet-Kin LeungShuk-Mei Ho
Oct 13, 2017·International Journal of Epidemiology·Janine F FelixStephanie J London
Sep 21, 2018·Epigenetics : Official Journal of the DNA Methylation Society·Xinyi LinNeerja Karnani
Mar 2, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Sophia HarlidJack A Taylor
Mar 18, 2019·International Journal of Epidemiology·Alexandra J WhiteJack A Taylor
Mar 19, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Aaron M MooreJack A Taylor
Feb 17, 2018·Epigenetics : Official Journal of the DNA Methylation Society·John DouKelly M Bakulski
Feb 23, 2019·Journal of the National Cancer Institute·Jacob K KresovichJack A Taylor
Apr 30, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Robin MyteSophia Harlid
Jun 23, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ayman AlhamdowKarin Broberg
Oct 11, 2019·Human Reproduction·Jacob K KresovichJack A Taylor
Jan 18, 2020·JAMA Network Open·Jacob K KresovichJack A Taylor
Apr 14, 2020·Journal of Alzheimer's Disease : JAD·Xiangzhu ZhuQi Dai
Jun 1, 2020·Human Reproduction·K W OlsenM L Grøndahl
Aug 5, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Zongli Xu, Jack A Taylor
Dec 19, 2019·Aging·Jacob K KresovichJack A Taylor
Sep 21, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Jonathan A HeissAllan C Just
Aug 18, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Yale JiangJuan C Celedón
Aug 18, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Christina A MarkunasJack A Taylor
May 10, 2020·The European Respiratory Journal·Thanh T HoangStephanie J London
Apr 17, 2019·Journal of the National Cancer Institute·Zongli XuJack A Taylor
Jun 30, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Nora Fernandez-JimenezMarie-France Hivert
Jan 11, 2019·Journal of Translational Medicine·Raúl F PérezEmpar Lurbe
Jun 6, 2019·Translational Psychiatry·Kaarina KowalecPatrick F Sullivan
May 5, 2020·Molecular Genetics and Genomics : MGG·Anil K GiriDwaipayan Bharadwaj
Apr 14, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Iolanda AgliataHector Hernandez-Vargas

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