Extended Data Fig. 6: Characterization of biological sources and composition of cfDNA variants.
From: High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants
(a) The bar plots show the number of somatic variants detected in plasma cfDNA per megabase (Mb, y-axis) for each sample (x-axis) stratified by cancer status and biological sources and ordered by increasing number of somatic WBC-matched variants. The panels show control samples (top left) and patients with MBC (top right), NSCLC (bottom left) and CRPC (bottom right). The colors indicate WBC-matched variants, tumor biopsy-matched variants, biopsy-subthreshold and VUSO. (b) Top mutated genes carrying WBC-matched variants for each cohort. The number in the cells indicate the overall number of variants for each gene in the corresponding cohort. In (a,b), the cohorts consist of n = 39 MBC, n = 41 NSCLC and n = 44 CRPC patients. Additionally, in (a) n = 47, non-cancer controls are shown. (c,d) Distribution of Variant Allele Fractions (VAFs) of somatic mutations detected in cfDNA and WBC using the high-intensity sequencing assay where variants are color coded according to source of origin. Somatic variants are displayed for n = 114 non-hypermutated cancer patients and n = 47 non-cancer controls. The allelic (AD) and total (DP) depths are obtained from raw pileups without base alignment quality filtering (BAQ). In (c), the VAF is smoothed with added pseudocounts to AD and DP such that \(AD^\prime = AD + 2\) and \(DP^\prime = DP + 4\). In (d), variants detected with zero AD in WBC were displayed as 0.01% VAF in WBC due to the logarithmic scaled axes.
