Extended Data Fig. 1: Simulations of non-invasive cancer detection based on number of alterations analysed and tumour-derived cfDNA fragment distributions.

a, Monte Carlo simulations were performed using different numbers of tumour-specific alterations to evaluate the probability of detecting cancer alterations in cfDNA at the indicated fraction of tumour-derived molecules. The simulations were performed assuming an average of 2,000 genome equivalents of cfDNA and the requirement of five or more observations of any alteration. These analyses indicate that increasing the number of tumour-specific alterations improves the sensitivity of detection of circulating tumour DNA. b, Cumulative density functions of cfDNA fragment lengths of 42 loci containing tumour-specific alterations from 30 patients with breast, colorectal, lung, or ovarian cancer are shown with 95% confidence bands (orange). Lengths of mutant cfDNA fragments were significantly different in size from wild-type cfDNA fragments (blue) at these loci. c, GC content was similar for mutated and non-mutated fragments. d, GC content was not correlated to fragment length.