Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Genet. 2016 Oct;48(10):1273-8. doi: 10.1038/ng.3648. Epub 2016 Aug 29.

Inferring expressed genes by whole-genome sequencing of plasma DNA.

Author information

1
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
2
Institute of Molecular Biotechnology, Graz University of Technology, Graz, Austria.
3
BioTechMed OMICS Center Graz, Graz, Austria.
4
Institute of Pathology, Medical University of Graz, Graz, Austria.
5
Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Abstract

The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing of plasma DNA and identified two discrete regions at transcription start sites (TSSs) where nucleosome occupancy results in different read depth coverage patterns for expressed and silent genes. By employing machine learning for gene classification, we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells. In patients with cancer having metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We were able to determine the expressed isoform of genes with several TSSs, as confirmed by RNA-seq analysis of the matching primary tumor. Our analyses provide functional information about cells releasing their DNA into the circulation.

PMID:
27571261
DOI:
10.1038/ng.3648
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center