Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, XXXX , and transplantation assessments.

@entity1 @entity706 @entity5 @entity9736 @entity157
UNASSIGNED: Plasma consists of DNA released from multiple tissues within the body. Using genome-wide @entity9736 sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant @entity1 , @entity1 with @entity157 , and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant @entity1 correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. @entity1 with @entity157 showed elevated plasma DNA contributions from the liver, which correlated with measurements made using @entity5 -associated copy number aberrations. In @entity157 @entity1 and in pregnant @entity1 exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant @entity1 diagnosed as having @entity706 during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma.
