Fig. 4: Whole-genome events and aneuploidy classes in HNSCC.
From: Inferring early genetic progression in cancers with unobtainable premalignant disease
a–c, Allelic copy number (CN) profiles after ABSOLUTE in example tumors with diploid (a), triploid (b) and tetraploid (c) profiles. Each locus has a blue line and a red line representing the copy numbers of the minor and major alleles, respectively. Histograms of raw MAF distributions among somatically mutated loci and corresponding MATH values (scale factor of k = 1.4826 for the median absolute deviation (MAD) of a normal distribution to equal its standard deviation) are shown. d, Comparison of whole-genome amplification timing determined from WES against that from WGS of the same tumors (N = 4). Each chromosome arm is timed individually and aggregated to determine the timing of the whole-genome event. Left, two tumors with a tetraploid profile. Right, two tumors with a triploid profile. Horizontal ticks represent means. Error bars represent 75% credible intervals from posterior sampling. Colors represent copy number states. e, Scatter plot of whole-genome amplification timings in WGS versus WES of 11 tumors. Boxes represent timing means. Error bars represent 75% credible intervals from posterior sampling; blue, tetraploid profile; yellow, triploid profile. f, Timing probability distributions across tumors (N = 216 whole-genome amplifications), on π scale, of whole-genome amplifications leading to tetraploid (WGD) and triploid (WGT) copy number profiles. g, Real-time timing of WGT and WGD events. Estimated conversion rate of WGD events into WGT per year with a Poisson-like model (red model and green data; N = 103 real-timed whole-genome amplifications). h, Real-time timing of main driver events in HPV+ (red) and HPV– (blue) tumors (N = 205 individuals with real-timed driver events). Arrows for somatic point mutations represent that the estimate is late bound by the time of the regional gain, but no early bound exists. HPV integration sites include early events and events occurring during the development of the tumor.
