Year: 2020
Type: article
Abstract: BACKGROUND: Cell-free DNA (cfDNA) in blood, urine, and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic sequencing. The total biomass of microbial-derived cfDNA in clinical isolates is low, which makes metagenomic cfDNA sequencing susceptible to contamination and alignment noise. RESULTS: Here, we report low biomass background correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high-throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection. CONCLUSIONS: The data provide unique insight into the properties of fetal and maternal cfDNA in amniotic fluid, demonstrate the utility of cfDNA to screen for intra-amniotic infection, support the view that the amniotic fluid is sterile during normal pregnancy, and reveal cases of intra-amniotic inflammation without infection at term. Video abstract.
Source: Microbiome
Institutions: Cornell University, United States Department of Health and Human Services, National Institutes of Health, Wayne State University, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NewYork–Presbyterian Hospital, Weill Cornell Medical Center, Detroit Medical Center, Michigan Medicine, Michigan State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, Wayne State University, Kenneth Rainin Foundation, Australian Government, Let's Beat Bowel Cancer, National Institutes of Health, National Science Foundation of Sri Lanka, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NHLBI Division of Intramural Research
Awards: G1252553166, G1284009618, G1348649281, G1985304581, G2671377752, Precision monitoring of kidney transplants via single-cell and single-molecule sequencing, G3252098559, G3268001613, G3388402394, G4176821937, Host-Pathogen Interactions From Measurements of Urinary Cell Free DNA in Kidney Transplantation, Gut Microbiome, Acute Rejection, and Tacrolimus Dosing in Kidney Transplantation, G4850583454, G5750123646, Biomolecular Markers for Safe Minimization of Immunosuppression, Graduate Reserach Fellowship Program (GRFP), Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell Transplantation, G7491476858, G810707897, Mitochondrial Cell-Free DNA as a Marker of Rejection and Damage-Associated Molecular Pattern in Organ Transplantation, G8649546003, G8887654449, Clinical and Translational Science Center, G974394604
OpenAlex ID: W3006410055