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Structure and diversity of urinary cell-free DNA informative of host-pathogen interactions in human urinary tract infection

Philip Burnham, Darshana Dadhania, Michael Heyang, Fanny Chen, Lars F. Westblade, View ORCID ProfileManikkam Suthanthiran, John Richard Lee, View ORCID ProfileIwijn De Vlaminck
doi: https://doi.org/10.1101/177402
Philip Burnham
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853
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Darshana Dadhania
2Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY 10065
3Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY 10065
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Michael Heyang
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853
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Fanny Chen
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853
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Lars F. Westblade
4Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York,NY 10065
5Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, NewYork, NY 10065
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Manikkam Suthanthiran
2Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY 10065
3Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY 10065
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  • ORCID record for Manikkam Suthanthiran
John Richard Lee
2Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY 10065
3Department of Transplantation Medicine, New York Presbyterian Hospital - Weill Cornell Medical Center, New York, NY 10065
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  • For correspondence: vlaminck@cornell.edu jrl2002@med.cornell.edu
Iwijn De Vlaminck
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853
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  • ORCID record for Iwijn De Vlaminck
  • For correspondence: vlaminck@cornell.edu jrl2002@med.cornell.edu
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Abstract

Infections of the urinary tract are the most common form of infection in the human population. Here, we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in the scope of bacterial and viral urinary tract infections. We assayed cfDNA isolated from 141 urine samples obtained from a cohort of 82 kidney transplant recipients by next-generation sequencing. We find that urinary cfDNA simultaneously informs about the composition of the bacterial and viral components of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and the host response to infection. These different layers of information are accessible from a single assay and individually agree with corresponding clinical tests based on quantitative PCR, conventional bacterial culture, and urinalysis. In addition, cfDNA reveals the frequent occurrence of pathologies that remain undiagnosed in conventional diagnostic workups. Our work identifies urinary cfDNA as a highly versatile tool to monitor infections of the urinary tract.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 16, 2018.
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Structure and diversity of urinary cell-free DNA informative of host-pathogen interactions in human urinary tract infection
Philip Burnham, Darshana Dadhania, Michael Heyang, Fanny Chen, Lars F. Westblade, Manikkam Suthanthiran, John Richard Lee, Iwijn De Vlaminck
bioRxiv 177402; doi: https://doi.org/10.1101/177402
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Structure and diversity of urinary cell-free DNA informative of host-pathogen interactions in human urinary tract infection
Philip Burnham, Darshana Dadhania, Michael Heyang, Fanny Chen, Lars F. Westblade, Manikkam Suthanthiran, John Richard Lee, Iwijn De Vlaminck
bioRxiv 177402; doi: https://doi.org/10.1101/177402

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