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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

By Meaghan J Jones, Louie Dinh, Hamid Reza Razzaghian, Olivia de Goede, Julia L. MacIsaac, Alexander M Morin, Kristina Gervin, Raymond Ng, Liesbeth Duijts, Menno C van Zelm, Henriƫtte A. Moll, Robert Lyle, Wendy P. Robinson, Devin C Koestler, Janine F. Felix, Pascal M Lavoie, Sara Mostafavi, Michael S Kobor

Posted 23 Aug 2018
bioRxiv DOI: 10.1101/399279

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 naive 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.

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