Beyond Sequence: Epigenomics, Fragmentomics, and Topology Expand Cell-Free DNA Analysis
This Science review by the pioneers of cell-free DNA analysis described how methylation patterns, fragment size distributions, end motifs, and topological forms (circular, single-stranded) of plasma DNA carry tissue-of-origin information beyond simple sequence variation. These multi-dimensional features are enabling next-generation liquid biopsy applications across prenatal testing, oncology, and transplant monitoring.
The original study
Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies.
- Authors
- Lo YMD, Han DSC, Jiang P, Chiu RWK
- Journal
- Science (New York, N.Y.)
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 33833097
Original abstract
Liquid biopsies that analyze cell-free DNA in blood plasma are used for noninvasive prenatal testing, oncology, and monitoring of organ transplant recipients. DNA molecules are released into the plasma from various bodily tissues. Physical and molecular features of cell-free DNA fragments and their distribution over the genome bear information about their tissues of origin. Moreover, patterns of DNA methylation of these molecules reflect those of their tissue sources. The nucleosomal organization and nuclease content of the tissue of origin affect the fragmentation profile of plasma DNA molecules, such as fragment size and end motifs. Besides double-stranded linear fragments, other topological forms of cell-free DNA also exist-namely circular and single-stranded molecules. Enhanced by these features, liquid biopsies hold promise for the noninvasive detection of tissue-specific pathologies with a range of clinical applications.