Extended Data Fig. 1: Genomic analysis of locally-advanced prostate cancer.
From: Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer
(A) Estimates of per-gene dN/dS for missense mutations only. dN/dS maximum likelihood estimates are calculated per gene by dNdScv. Intervals represent 95% confidence level, the bars represent the maximum likelihood estimate and dotted line represents dNdS = 1 (neutral). Missense mutations are positively selected in SPOP, TP53 and FOXA1 as the lower bounds of the intervals are greater than 1. (B) Estimates of per-gene dN/dS for truncating mutations only. Intervals represent 95% confidence level, the bars represent the maximum likelihood estimate and dotted line represents dNdS = 1 (neutral). Truncating mutations are positively selected in CDKN1B and TP53. Number of mutation types per gene are provided in source material. (C) A heatmap of per sample absolute copy number calls. Chromosomes are represented on the x-axis and samples are grouped by participant on the y-axis, separated by lines (n = 609 samples, n = 114 participants). Copy numbers are not normalised relative to baseline ploidy. (D) DNA damage mutations versus mean PGA. Boxplots represent mean PGA (mPGA) separated based on the clonality of mutations involved in DNA damage response (TP53, ATM, BRCA1/2, CDK12, PALB2). The status is considered clonal if any of the mutations are detected in all samples. mPGA is significantly higher in participants with a clonal DNA damage mutation compared to participants with no DNA damage mutations (2-sided t-test, standard error = 0.055, d.f. = 10.1, t = 2.94). Mutations are split into clonal (n = 10 participants), subclonal (n = 13 participants) and wild-type (n = 75 participants). Boxplots show centre line as median, box limits as upper and lower quartiles, whiskers extend no further than 1.5x interquartile range past the box limits and points represent outliers. (E) Distribution of Spearman values for cohort (n = 106 participants) used for outcome analysis displays a long tail of high values that are discriminated by a threshold of the upper tertile (dotted line).
