RT Journal Article SR Electronic T1 Inferring expressed genes by whole-genome sequencing of plasma DNA JF bioRxiv FD Cold Spring Harbor Laboratory SP 049478 DO 10.1101/049478 A1 Peter Ulz A1 Gerhard G. Thallinger A1 Martina Auer A1 Ricarda Graf A1 Karl Kashofer A1 Stephan W. Jahn A1 Luca Abete A1 Gunda Pristauz A1 Edgar Petru A1 Jochen B. Geigl A1 Ellen Heitzer A1 Michael R. Speicher YR 2016 UL http://biorxiv.org/content/early/2016/04/20/049478.abstract AB 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 (WGS) of plasma DNA and identified two discrete regions at transcription start sites (TSS) where the nucleosome occupancy results in different read-depth coverage patterns in 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 cancer patients with metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We could even determine the expressed isoform of genes with several TSSs as confirmed by RNA-Seq of the matching primary tumor. Our analyses provide functional information about the cells releasing their DNA into the circulation.