DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used to identify libraries for deconvolution of DNA methylation data for current and previous platforms. The accuracy of deconvolution estimates obtained using our enhanced libraries was validated using artificial mixtures and whole-blood DNA methylation with known cellular composition from flow cytometry. We applied our libraries to deconvolve cancer, aging, and autoimmune disease datasets. In conclusion, these libraries enable a detailed representation of immune-cell profiles in blood using only DNA and facilitate a standardized, thorough investigation of immune profiles in human health and disease. Deconvolution algorithms facilitate studying cell type-specific changes using bulk data from complex tissues. Here, the authors present a deconvolution method that predicts DNA methylation levels in 12 leukocyte subtypes using human microarray data and apply it to various examples.
【저자키워드】 Translational research, Microarrays, DNA methylation, Epigenetics in immune cells, 【초록키워드】 Neutrophils, Monocytes, Cancer, memory B cells, Immune profile, flow cytometry, memory, Autoimmune disease, DNA, Health, Accuracy, cells, eosinophils, Algorithm, Microarray, estimate, disease, change, predict, Blood, basophils, cellular, leukocyte, natural killer, tissues, profile, complex, naïve, datasets, T regulatory cells, subtype, Cell, identify, was used, include, applied, facilitate, provide, expand, DNA methylation level, immune-cell, Including, variables, 【제목키워드】 Peripheral blood, immune profiling, High-resolution, enhanced, Cell,