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

• Published in: Genome Biology Vol. 19; no. 1; p. 64
• Main Authors: Salas, Lucas A., Koestler, Devin C., Butler, Rondi A., Hansen, Helen M., Wiencke, John K., Kelsey, Karl T., Christensen, Brock C.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 29.05.2018; Springer Nature B.V; BMC
• Subjects: Accuracy; Algorithms; Animal Genetics and Genomics; B-cells; B-lymphocytes; Bioinformatics; Biomedical and Life Sciences; Blood; Blood Cells - metabolism; CD4 antigen; CD8 antigen; CD8-positive T-lymphocytes; CpG Islands; Datasets; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenetics; Ethnicity; Evolutionary Biology; Gene expression; Gene Library; Genetic testing; genome; Genomes; Human Genetics; Humans; Life Sciences; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Method; Microbial Genetics and Genomics; Monocytes; Natural killer cells; Neutrophils; Oligonucleotide Array Sequence Analysis; Plant Genetics and Genomics; B-cells; Monocytes; Helper T-cells; Cytotoxic T-lymphocytes; Neutrophils; DNA methylation; Epigenetics; Adults; Natural killer cells; Leukocytes
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-018-1448-7

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 R 2  = 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.