TY  - BOOK
AU  - Oza, Kesha
TI  - Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant
PY  - 2024///
KW  - Automated
KW  - MedStar General Surgery Residency
KW  - MedStar Georgetown University Hospital/MedStar Washington Hospital Center
KW  - Preprint
N2  - Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention
UR  - https://dx.doi.org/10.1101/2024.04.04.588176
ER  -