PT  - JOURNAL ARTICLE
AU  - Meaghan J Jones
AU  - Louie Dinh
AU  - Hamid Reza Razzaghian
AU  - Olivia de Goede
AU  - Julia L MacIsaac
AU  - Alexander M. Morin
AU  - Kristina Gervin
AU  - Raymond Ng
AU  - Liesbeth Duijts
AU  - Menno C van Zelm
AU  - Henriëtte A Moll
AU  - Robert Lyle
AU  - Wendy P Robinson
AU  - Devin C Koestler
AU  - Janine F Felix
AU  - Pascal M Lavoie
AU  - Sara Mostafavi
AU  - Michael S Kobor
TI  - Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction
AID  - 10.1101/399279
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 399279
4099  - http://biorxiv.org/content/early/2018/08/23/399279.short
4100  - http://biorxiv.org/content/early/2018/08/23/399279.full
AB  - Background DNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.Results Though all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.Conclusion Changes in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.