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

TLDR

Plasma DNA originates from multiple tissues in the body. The study uses genome‑wide bisulfite sequencing of plasma DNA to map the identities and contributions of tissues to the circulating DNA pool. A bioinformatics deconvolution of methylation signatures identifies tissue contributors and their proportions, validated in pregnant women, cancer patients, and transplant recipients. The method identifies tissue origins of plasma DNA aberrations and has broad applications in prenatal testing, oncology, and transplantation monitoring.

Abstract

Significance Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA, we obtained a bird’s eye view of the identities and contributions of these tissues to the circulating DNA pool. The tissue contributors and their relative proportions are identified by a bioinformatics deconvolution process that draws reference from DNA methylation signatures representative of each tissue type. We validated this approach in pregnant women, cancer patients, and transplant recipients. This method also allows one to identify the tissue of origin of genomic aberrations observed in plasma DNA. This approach has numerous research and diagnostic applications in prenatal testing, oncology, transplantation monitoring, and other fields.