Fig. 8: Estimating tumor age.

A The empirical \({{\rm{\beta }}}\)-value distributions of the 500 fCpG sites in the clock set are decomposed into three peaks corresponding to initially unmethylated (blue), hemi-methylated (yellow), and fully methylated (red) sites. B Tumor mitotic age (the number of generations) is shown for the TCGA and Lund cohorts and colored by molecular subtype. These estimates are based on the peak locations (panel A) and a (de-)methylation rate of \({{\rm{\mu }}}=2\cdot {10}^{-3}\), per cell division and per allele, which yields a mean tumor age of 3 calendar years (see E). C For the Lund cohort, tumor-specific proliferation rates are estimated using the measured fraction of cells in S-phase and shown by molecular subtype. D For the TCGA cohort, proliferation rates are estimated using S-phase fractions predicted based on gene expression, using a model trained on the Lund cohort. E Calendar age of tumors in the TCGA and Lund cohorts, colored by molecular subtype. Boxplots in C and D display: center line, median; box limits, upper and lower quartiles; whiskers, 1.5x interquartile range; points, outliers.