Implementation of our approach using plasma DNA samples from individuals without cancer and simulations. (a) Z-scores calculated for sequential 1-Mbp windows for 10 male (upper panel) and 9 female (lower panel) individuals without malignant disease. (b) Detection of tumor DNA in plasma from patients with prostate cancer using simulated copy-number analyses. ROC analyses of simulated mixtures of prostate cancer DNA with normal plasma DNA using the genome-wide z-score. Detection of 10% circulating tumor DNA could be achieved with a sensitivity of >80% and specificity of >80%. (c) Hierarchical cluster analysis (Manhattan distances of chromosomal z-scores) with normal female controls and the HT29 serial dilution series. One percent of tumor DNA still had an increased genome-wide z-score and did not cluster together with the controls (for details see text).