title: Inferring expressed genes by whole-genome sequencing of plasma DNA.
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.
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Peter
authors: 0000-0001-5941-1160
authors: P
authors: Ulz
authors: Institute of Molecular Biotechnology, Graz University of Technology, Graz, Austria.|BioTechMed OMICS Center Graz, Graz, Austria.
authors: Gerhard G
authors: GG
authors: Thallinger
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Martina
authors: M
authors: Auer
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Ricarda
authors: R
authors: Graf
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: Karl
authors: K
authors: Kashofer
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: Stephan W
authors: SW
authors: Jahn
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: Luca
authors: L
authors: Abete
authors: Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
authors: Gunda
authors: G
authors: Pristauz
authors: Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
authors: Edgar
authors: E
authors: Petru
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Jochen B
authors: JB
authors: Geigl
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Ellen
authors: E
authors: Heitzer
authors: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: Michael R
authors: 0000-0003-0105-955X
authors: MR
authors: Speicher
mesh_terms: D004247:DNA / Q000097:blood*; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics; D012313:RNA / Q000097:blood; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site
chemical_list: D009707:Nucleosomes; D012313:RNA; D004247:DNA