Skip to main content
New Results

# Sub-nucleosomal organization in urine cell-free DNA

Havell Markus, Jun Zhao, Tania Contente-Cuomo, View ORCID Profile Elizabeth Raupach, Ahuva Odenheimer-Bergman, Sydney Connor, Bradon R. McDonald, Elizabeth Hutchins, Marissa McGilvery, Michelina C. de la Maza, Kendall Van Keuren-Jensen, Patrick Pirrotte, Ajay Goel, Carlos Becerra, Daniel D. Von Hoff, Scott A. Celinski, Pooja Hingorani, View ORCID Profile Muhammed Murtaza
doi: https://doi.org/10.1101/696633
Havell Markus
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Jun Zhao
Translational Genomics Research Institute, Phoenix, AZ, USAPhoenix Children’s Hospital, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Tania Contente-Cuomo
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Elizabeth Raupach
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site
- ORCID record for Elizabeth Raupach

Ahuva Odenheimer-Bergman
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Sydney Connor
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Bradon R. McDonald
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Elizabeth Hutchins
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Marissa McGilvery
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Michelina C. de la Maza
Phoenix Children’s Hospital, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Kendall Van Keuren-Jensen
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Patrick Pirrotte
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Ajay Goel
Baylor Scott & White Research Institute, Baylor University Medical Center, Dallas, TX, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Carlos Becerra
Baylor Scott & White Research Institute, Baylor University Medical Center, Dallas, TX, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Daniel D. Von Hoff
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Scott A. Celinski
Baylor Scott & White Research Institute, Baylor University Medical Center, Dallas, TX, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Pooja Hingorani
Phoenix Children’s Hospital, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site

Muhammed Murtaza
Translational Genomics Research Institute, Phoenix, AZ, USA

- Find this author on Google Scholar
- Find this author on PubMed
- Search for this author on this site
- ORCID record for Muhammed Murtaza
- For correspondence: mmurtaza@tgen.org

- Abstract
- Full Text
- Info/History
- Metrics
- Supplementary material
- Preview PDF

## Abstract

Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented and whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we perform comprehensive characterization of fragmentation patterns in urine cfDNA. We show modal size and genome-wide distribution of urine cfDNA fragments are consistent with transient protection from degradation by stable intermediates of nucleosome disassembly. Genome-wide nucleosome occupancy and fragment sizes in urine cfDNA are informative of cell of origin and renal epithelial cells are amongst the highest contributors in urine. Compared to a nucleosome occupancy map based on control urine samples, we observe a higher fraction of fragments with aberrant ends in cancer patients, distinguishing cancer samples with an area under the curve of 0.89. Our results demonstrate sub-nucleosomal organization in urine cfDNA and are proof-of-principle that genome-wide fragmentation analysis of urine cfDNA can enable cancer diagnostics.

Copyright
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-NC-ND 4.0 International license.
Back to top
Previous Next
Posted July 11, 2019.
Download PDF

Supplementary Material

Email
Share
Sub-nucleosomal organization in urine cell-free DNA
Havell Markus, Jun Zhao, Tania Contente-Cuomo, Elizabeth Raupach, Ahuva Odenheimer-Bergman, Sydney Connor, Bradon R. McDonald, Elizabeth Hutchins, Marissa McGilvery, Michelina C. de la Maza, Kendall Van Keuren-Jensen, Patrick Pirrotte, Ajay Goel, Carlos Becerra, Daniel D. Von Hoff, Scott A. Celinski, Pooja Hingorani, Muhammed Murtaza
bioRxiv 696633; doi: https://doi.org/10.1101/696633
Share This Article:
Citation Tools
Sub-nucleosomal organization in urine cell-free DNA
Havell Markus, Jun Zhao, Tania Contente-Cuomo, Elizabeth Raupach, Ahuva Odenheimer-Bergman, Sydney Connor, Bradon R. McDonald, Elizabeth Hutchins, Marissa McGilvery, Michelina C. de la Maza, Kendall Van Keuren-Jensen, Patrick Pirrotte, Ajay Goel, Carlos Becerra, Daniel D. Von Hoff, Scott A. Celinski, Pooja Hingorani, Muhammed Murtaza
bioRxiv 696633; doi: https://doi.org/10.1101/696633

## Citation Manager Formats

- BibTeX
- Bookends
- EasyBib
- EndNote (tagged)
- EndNote 8 (xml)
- Medlars
- Mendeley
- Papers
- RefWorks Tagged
- Ref Manager
- RIS
- Zotero

- Tweet Widget
- Facebook Like
- Google Plus One

## Subject Area

- Genomics

Subject Areas
All Articles

- Animal Behavior and Cognition (1266)
- Biochemistry (2038)
- Bioengineering (1405)
- Bioinformatics (8492)
- Biophysics (3282)
- Cancer Biology (2437)
- Cell Biology (3470)
- Clinical Trials (132)
- Developmental Biology (2200)
- Ecology (3420)
- Epidemiology (1988)
- Evolutionary Biology (6034)
- Genetics (4515)
- Genomics (5716)
- Immunology (1728)
- Microbiology (5788)
- Molecular Biology (2228)
- Neuroscience (14352)
- Paleontology (103)
- Pathology (340)
- Pharmacology and Toxicology (586)
- Physiology (840)
- Plant Biology (2016)
- Scientific Communication and Education (532)
- Synthetic Biology (708)
- Systems Biology (2352)
- Zoology (356)