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%0 Thesis
%A Bocova, Ledio
%T DNA methylation biomarkers for deconvolution of hematopoietic subsets in clinical settings
%I RWTH Aachen University
%V Dissertation
%C Aachen
%M RWTH-2024-05868
%P 1 Online-Ressource : Illustrationen
%D 2024
%Z Veröffentlicht auf dem Publikationsserver der RWTH Aachen University
%Z Dissertation, RWTH Aachen University, 2024
%X Hematopoietic differentiation is associated with DNA methylation (DNAm) changes at specific sites in the genome. Our group has previously shown that these epigenetic changes provide a powerful perspective to determine the cellular composition in blood. We established Epi-Blood-Count, for leukocyte quantification based on targeted DNAm analysis at individual cell-specific CG dinucleotides (CpG sites). In contrast to classical methods, it is not based on expression markers, thus enabling differential blood counts in cryopreserved blood samples. The aim of this thesis was to further optimize and validate Epi-blood-Count for clinical applications. To this end, samples from healthy individuals and from patients with hematological disorders that are known to have aberrant DNAm were analyzed. The DNAm at CpGs for granulocytes, monocytes, lymphocytes, CD4 T cells, CD8 T cells, B cells and NK cells were measured with pyrosequencing and digital droplet PCR (ddPCR) and with both methods, epigenetic leukocyte counts correlated strongly with conventional leukocyte counts. In some patients with hematological malignancies, we observed outliers in epigenetic leukocyte counts, which could be identified if the relative proportions of leukocyte subsets did not sum up to 100
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%R 10.18154/RWTH-2024-05868
%U https://publications.rwth-aachen.de/record/987837