title: RELIC: a novel dye-bias correction method for Illumina Methylation BeadChip.
abstract: The Illumina Infinium HumanMethylation450 BeadChip and its successor, Infinium MethylationEPIC BeadChip, have been extensively utilized in epigenome-wide association studies. Both arrays use two fluorescent dyes (Cy3-green/Cy5-red) to measure methylation level at CpG sites. However, performance difference between dyes can result in biased estimates of methylation levels.
  
  
  
  Here we describe a novel method, called REgression on Logarithm of Internal Control probes (RELIC) to correct for dye bias on whole array by utilizing the intensity values of paired internal control probes that monitor the two color channels. We evaluate the method in several datasets against other widely used dye-bias correction methods. Results on data quality improvement showed that RELIC correction statistically significantly outperforms alternative dye-bias correction methods. We incorporated the method into the R package ENmix, which is freely available from the Bioconductor website ( https://www.bioconductor.org/packages/release/bioc/html/ENmix.html ).
  
  
  
  RELIC is an efficient and robust method to correct for dye-bias in Illumina Methylation BeadChip data. It outperforms other alternative methods and conveniently implemented in R package ENmix to facilitate DNA methylation studies.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Environmental Risk and Health unit, Flemish Institute for Technological Research (VITO), Mol, Belgium.|Faculty of Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Sabine A S
authors.initials: SA
authors.lastname: Langie
authors.affiliation: Environmental Risk and Health unit, Flemish Institute for Technological Research (VITO), Mol, Belgium.|Faculty of Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.|Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Taylor
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. niulg@ucmail.uc.edu.
authors.forename: Liang
authors.identifier: 0000-0002-2473-9745
authors.initials: L
authors.lastname: Niu
mesh_terms: D019295:Computational Biology / Q000379:methods* / Q000592:standards; D019175:DNA Methylation; D066264:Datasets as Topic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000592:standards; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D012984:Software; D064878:Web Browser
keywords: DNA methylation; Data preprocessing; Dye-bias correction; Illumina HumanMethylation450; Illumina MethylationEPIC; RELIC