RT Journal Article SR Electronic T1 Inference of tumor cell-specific transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection of cancer JF bioRxiv FD Cold Spring Harbor Laboratory SP 456681 DO 10.1101/456681 A1 Peter Ulz A1 Samantha Perakis A1 Qing Zhou A1 Tina Moser A1 Jelena Belic A1 Isaac Lazzeri A1 Albert Wölfler A1 Armin Zebisch A1 Armin Gerger A1 Gunda Pristauz A1 Edgar Petru A1 Brandon White A1 Charles E.S. Roberts A1 John St. John A1 Michael G. Schimek A1 Jochen B. Geigl A1 Thomas Bauernhofer A1 Heinz Sill A1 Christoph Bock A1 Ellen Heitzer A1 Michael R. Speicher YR 2019 UL http://biorxiv.org/content/early/2019/03/31/456681.abstract AB Deregulation of transcription factors (TFs) is an important driver of tumorigenesis. We developed and validated a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyzed whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a newly developed bioinformatics pipeline that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observed patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of early detection of colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.