An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray

• Main Authors: Lucas A. Salas, Devin C. Koestler, Rondi A. Butler, Helen M. Hansen, John K. Wiencke, Karl T. Kelsey, Brock C. Christensen
• Format: Article
• Language: English
• Published: BMC 2018-05-01
• Series: Genome Biology
• Subjects: DNA methylation; Epigenetics; Neutrophils; Monocytes; Natural killer cells; B-cells
• Online Access: http://link.springer.com/article/10.1186/s13059-018-1448-7

Abstract Genome-wide methylation arrays are powerful tools for assessing cell composition of complex mixtures. We compare three approaches to select reference libraries for deconvoluting neutrophil, monocyte, B-lymphocyte, natural killer, and CD4+ and CD8+ T-cell fractions based on blood-derived DNA methylation signatures assayed using the Illumina HumanMethylationEPIC array. The IDOL algorithm identifies a library of 450 CpGs, resulting in an average R2 = 99.2 across cell types when applied to EPIC methylation data collected on artificial mixtures constructed from the above cell types. Of the 450 CpGs, 69% are unique to EPIC. This library has the potential to reduce unintended technical differences across array platforms.