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 May 16, 2026)
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Plasma contains ultrashort single-stranded DNA in addition to nucleosomal cell-free DNA
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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
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Keywords
DNA, liquid biopsy: cell free, cancer
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Created July 8, 2022, Updated March 16, 2023