A cell-type specific human methylome atlas

Methylation patterns in circulating cell-free DNA (cfDNA) can be traced back to their tissue of origin and to provide important information about cell death rates in specific human tissue in health and disease. We have previously shown that the tissue origins of cfDNA can be inferred using an extensive atlas of tissue-specific methylomes. However, since human tissues are a composite of multiple cell types, bulk methylomes do not provide information about rare cell types such as pancreatic beta cells or about common cell types such as vascular endothelial cells. To generate a human cell-type methylome atlas we have established a pipeline for dissociation of fresh human surgical material, sorting of cell types of interest, deep whole genome bisulfite sequencing, and comparative methylome analysis. Initial analysis of this ongoing project support the utility of cell-type methylomes for high-resolution interpretation of cfDNA methylation towards early diagnosis of disease. In addition, the atlas provides insights into epigenetic similarities and differences between cell subtypes, such as epithelial cells of adjacent segments of the intestine, and vascular endothelial cells from different organs.