NK NK NK NK CD8T CD8T CD8T CD8T CD8T CD8T CD4T CD4T CD4T CD4T CD4T CD4T Gran Gran Gran Gran Gran Gran Bcell Bcell Bcell Bcell Bcell Bcell Mono Mono Mono Mono Mono Mono CpGs Cell types Whole blood cell types: • Tcells • CD8T • CD4T • Natural Killer • Bcells • Granulocytes • Monocytes Bioconductor data package available: • Data originally from Reinius et al. (2012) > library(FlowSorted.Blood.450k)
in whole blood imply different observed whole blood DNA methylation profiles • Important to estimate differences in cell composition Cell composition changes with age
k=1 K ∑ X jk +εij = + Y (Jx1) X (JxK) = E (Jx1) π (Kx1) J CpGs K cell type profiles whole blood sample i = (1,..., N) = whole blood samples j = (1,...., J) = CpGs k = (1,...,K) = cell type profiles Measurement error relative cell type proportions NK NK NK NK NK NK CD8T CD8T CD8T CD8T CD8T CD8T CD4T CD4T CD4T CD4T CD4T CD4T Gran Gran Gran Gran Gran Gran Bcell Bcell Bcell Bcell Bcell Bcell Mono Mono Mono Mono Mono Mono
using new platform technology Problems with this approach 1. Not all CpGs are included in new platforms 2. Observed methylation levels depend on platform used
using new platform technology Problems with this approach 1. Not all CpGs are included in new platforms 2. Observed methylation levels depend on platform used