Fig. 3
From: Correlation of an epigenetic mitotic clock with cancer risk
The pcgtAge/epiTOC model approximates a mitotic clock. a The x-axis labels the cumulative total number of stem cell divisions (TNSC) incurred per stem cell in the given normal tissue in a log2 scale. This number is the log2 of the product of the intrinsic rate of cell divisions per year per stem cell (tissue-dependent) with the chronological age of the sample (tissue-independent). The y-axis labels the pcgtAge score of the sample. Samples have been colored according to the normal tissue of origin (normal samples adjacent to TCGA cancer types, as indicated). The number of normal samples for each tissue is given. Samples are seen to cluster into three main groups: a low cellular turnover group, a medium cellular turnover group, and a high cellular turnover group (note that this grouping is inferred from the unlogged scale, as shown in b). b Same as panel a but with TNSC shown in the unlogged scale. The P value is from a linear regression adjusted for chronological age of samples. c As b but for Horvath’s age-acceleration measure (i.e., DNAmAge minus chronological age). The P value is from a linear regression (already adjusted for age from the definition of age acceleration). d pcgtAge scores for the three different turnover groups as shown in a and b. The P values are from comparing the neighboring groups using a one-tailed Wilcoxon rank sum test, adjusted for chronological age. e As d but for Horvath’s age-acceleration measure. f The Pearson correlation coefficient (PCC) between either pcgtAge or Horvath’s age-acceleration measure, with an mRNA expression-based mitotic index, as estimated over all cancer samples of a given cancer type for a total of 15 different TCGA cancer types. Thus, each boxplot has 15 data points. The P value is from a one-tailed paired Wilcoxon rank sum test. g Corresponding heat map indicating for which cancer types there was a significant positive PCC between pcgtAge or Horvath’s AgeAccel with the mRNA expression-based mitotic index. The binomial test P value indicates that pcgtAge correlates more strongly with the mitotic index than Horvath’s age-acceleration measure