Plasma contains ultrashort single-stranded DNA in addition to nucleosomal cell-free DNA

Published

July 8, 2022

Author(s)

Hua-Jun He, Kenneth D. Cole

Abstract

Plasma cell-free DNA is being widely explored as a biomarker for clinical screening. Currently, methods are optimized for the extraction and detection of double-stranded mononucleosomal cell-free DNA of ∼160bp in length. We introduce uscfDNA-seq, a single-stranded cell-free DNA next-generation sequencing pipeline, which bypasses previous limitations to reveal a population of ultrashort single-stranded cell-free DNA in human plasma. This species has a modal size of 50nt and is distinctly separate from mononucleosomal cell-free DNA. Treatment with single-stranded and double-stranded specific nucleases suggests that ultrashort cell-free DNA is primarily single-stranded. It is distributed evenly across chromosomes and has a similar distribution profile over functional elements as the genome, albeit with an enrichment over promoters, exons, and introns, which may be suggestive of a terminal state of genome degradation. The examination of this cfDNA species could reveal new features of cell death pathways or it can be used for cell-free DNA biomarker discovery.

Citation

iSCIENCE

Volume

25

Issue

7

Pub Type

Journals

Download Paper

https://doi.org/10.1016/j.isci.2022.104554

Local Download

Keywords

DNA, liquid biopsy: cell free, cancer

Citation

He, H. and Cole, K. (2022), Plasma contains ultrashort single-stranded DNA in addition to nucleosomal cell-free DNA, iSCIENCE, [online], https://doi.org/10.1016/j.isci.2022.104554, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=933295 (Accessed October 13, 2025)