title: RCP: a novel probe design bias correction method for Illumina Methylation BeadChip.
abstract: The Illumina HumanMethylation450 BeadChip has been extensively utilized in epigenome-wide association studies. This array and its successor, the MethylationEPIC array, use two types of probes-Infinium I (type I) and Infinium II (type II)-in order to increase genome coverage but differences in probe chemistries result in different type I and II distributions of methylation values. Ignoring the difference in distributions between the two probe types may bias downstream analysis.
  
  
  
  Here, we developed a novel method, called Regression on Correlated Probes (RCP), which uses the existing correlation between pairs of nearby type I and II probes to adjust the beta values of all type II probes. We evaluate the effect of this adjustment on reducing probe design type bias, reducing technical variation in duplicate samples, improving accuracy of measurements against known standards, and retention of biological signal. We find that RCP is statistically significantly better than unadjusted data or adjustment with alternative methods including SWAN and BMIQ.
  
  
  
  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).
  
  
  
  niulg@ucmail.uc.edu
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Niu
authors.affiliation: Epidemiology Branch.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Epidemiology Branch 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
mesh_terms: D015982:Bias; D019175:DNA Methylation; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D015341:Nucleic Acid Probes; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D015341:Nucleic Acid Probes