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. 2024 May 17;15:4211. doi: 10.1038/s41467-024-48649-8

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Violins display the distribution of stemTOC’s mitotic age for normal tissue (N) and age-matched precancerous (PreC) samples for 9 different DNAm datasets. Number of samples in each category is displayed below x-axis, as well as the tissue-type and the nature of the precancerous sample. DCIS ductal carcinoma in situ, PreM premalignant, OLP oral lichen planus, LCIS lung carcinoma in situ. P-value derives from a one-tailed Wilcoxon rank sum test. b Top: Violin plots depicting the estimated epithelial and immune cell fraction in 790 buccal swabs from women all aged-53 at sample draw. Bottom left: Scatterplot of stemTOC (y-axis) against estimated squamous epithelial fraction (x-axis) for the same 790 buccal swabs. Samples are colored by their lifelong smoking habit (current, ex-smoker, and never-smoker). Two-tailed P-value is from a multivariate linear regression including epithelial fraction and smoking status. Bottom right: Violin plots display stemTOC versus smoking status. Two-tailed P-value is from a multivariate linear regression including smoking status and squamous epithelial fraction. c Top: Violins display the estimated cell-type fraction for 7 lung cell types (Endo endothelial, Epi epithelial, Gran granulocyte, Lym lymphocyte, Macro macrophage, Mono monocyte, Stromal) in 204 normal lung samples from eGTEX. Bottom: Violin plots display stemTOC versus chronological age and smoking status in the same 204 normal lung-tissue samples. Number of samples in each smoking category and age-group is shown below each box. Violin colors label smoking status as in (b). Two-tailed P-values for age and smoking status are derived from a multivariate linear regression that included age, smoking, and lung epithelial fraction. d Top left: Violins of estimated cell-type fractions for 5 cell types (Hep hepatocytes, Chol cholangiocytes, EC endothelial cells, Kup Kupffer cells, Lym lymphocytes) in 325 liver samples. Top right: Violins of the hepatocyte fraction against NAFLD disease stage. Two-tailed P-value is from a linear regression. Middle: Scatterplot of stemTOC (y-axis) against chronological age (x-axis) for the same 325 liver samples, with colors labeling the stage of NAFLD, with color label as in the previous panel. Bottom: Violin plots display mitotic age against NAFLD stage. Two-tailed P-value for disease stage derives from a multivariate linear regression that included age and hepatocyte fraction. Generated with Biorender.com.