High-resolution profiling of human cytomegalovirus cell-free DNA in human plasma highlights its exceptionally fragmented nature.

Autor:	Peddu V; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Bradley BT; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Casto AM; Department of Medicine, University of Washington, Seattle, WA, USA., Shree R; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA., Colbert BG; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Xie H; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Santo TK; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Huang ML; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Cheng EY; Department of Medicine, University of Washington, Seattle, WA, USA., Konnick E; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Salipante SJ; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Jerome KR; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.; Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Lockwood CM; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA., Greninger AL; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. agrening@uw.edu.; Fred Hutchinson Cancer Research Center, Seattle, WA, USA. agrening@uw.edu.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2020 Feb 28; Vol. 10 (1), pp. 3734. Date of Electronic Publication: 2020 Feb 28.
DOI:	10.1038/s41598-020-60655-6
Abstrakt:	Human cytomegalovirus (CMV) infections comprise a leading cause of newborn impairments worldwide and are pervasive concerns among the immunocompromised. Quantification of CMV viral loads is increasingly used to guide definitions of CMV disease but standardization of CMV quantitation remains problematic, mostly due to differences in qPCR amplicon sizes between clinical laboratories. Here, we used plasma cfDNA sequencing data from 2,208 samples sent for non-invasive prenatal aneuploidy screening to detect CMV and precisely measure the length of CMV fragments in human plasma. CMV reads were identified in 120 (5.4%) samples. Median cfDNA fragment size derived from CMV was significantly shorter than cfDNA derived from human chromosomes (103 vs 172 bp, p < 0.0001), corresponding to the 3 rd percentile of human cfDNA. Sequencing of cfDNA from seven plasma samples from transplant patients positive for CMV confirmed the extraordinarily short nature of CMV cfDNA fragment size with a median length of 149 bp. We further show that these high-resolution measurements of CMV DNA fragment size accurately predict measured discrepancies in serum viral load measurements by different qPCR assays. These results highlight the exceptionally fragmented nature of CMV cfDNA and illustrate the promise of plasma cfDNA sequencing for quantitating viral loads through detection of fragments that would be unrecoverable by qPCR.
Databáze:	MEDLINE
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