Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array

Lisa M Mcewen (1) , Meaghan Jones (1) , David Tse Shen Lin (1) , Rachel D Edgar (1) , Lucas T Husquin (2) , Julia L Macisaac (1) , Katia E Ramadori (1) , Alexander M Morin (1) , Christopher F Rider (3) , Chris Carlsten (3) , Lluis Quintana-Murci (2) , Steve Horvath (4) , Michael S Kobor (1)

1 BCCHR - BC Children's Hospital Research Institute [Vancouver, BC, Canada]
2 Génétique Evolutive Humaine - Human Evolutionary Genetics
3 University of British Columbia [Vancouver]
4 UCLA - University of California [Los Angeles]

Background: The capacity of technologies measuring DNA methylation (DNAm) is rapidly evolving, as are the options for applicable bioinformatics methods. The most commonly used DNAm microarray, the Illumina Infinium HumanMethylation450 (450K array), has recently been replaced by the Illumina Infinium HumanMethylationEPIC (EPIC array), nearly doubling the number of targeted CpG sites. Given that a subset of 450K CpG sites is absent on the EPIC array and that several tools for both data normalization and analyses were developed on the 450K array, it is important to assess their utility when applied to EPIC array data. One of the most commonly used 450K tools is the pan-tissue epigenetic clock, a multivariate predictor of biological age based on DNAm at 353 CpG sites. Of these CpGs, 19 are missing from the EPIC array, thus raising the question of whether EPIC data can be used to accurately estimate DNAm age. We also investigated a 71-CpG epigenetic age predictor, referred to as the Hannum method, which lacks 6 probes on the EPIC array. To evaluate these epigenetic clocks in EPIC data properly, a prior assessment of the effects of data preprocessing methods on DNAm age is also required.

Mots clés: Preprocessing; 450K; DNA methylation; DNA methylation age; EPIC; Epigenetic age; Epigenetic clock; Human; Microarray

Domaines: Génétique humaine; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Lisa M Mcewen, Meaghan Jones, David Tse Shen Lin, Rachel D Edgar, Lucas T Husquin, et al.. Systematic evaluation of DNA methylation age estimation with common preprocessing methods and the Infinium MethylationEPIC BeadChip array. Clinical Epigenetics, 2018, 10 (1), pp.123. ⟨10.1186/s13148-018-0556-2⟩. ⟨pasteur-02550471⟩