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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. 2 — a For selected normal-adjacent tissue-types, scatterplots of stemTOC’s mitotic age (y-axis) vs chronological age (x-axis). Number of normal-adjacent samples is given above each plot. The Pearson Correlation Coefficient (PCC) and two-tailed P-value from a linear regression are given. Normal-adjacent tissue-types in TCGA are labeled by the corresponding cancer type. b Heatmap of PCC values between mitotic and chronological age for 7 mitotic clocks and across all normal-adjacent tissue-types from the TCGA. Two-tailed P-values are from the linear regression test. Number of normal-adjacent samples for tissue-types not shown in (a) are: CHOL(n = 9), KIRP(n = 45), THCA(n = 56), HNSC(n = 50), BLCA(n = 21), PAAD(n = 10), PRAD(n = 50), ESCA(n = 16). c As (a), but for three sorted immune-cell populations as profiled by BLUEPRINT. d As (b) but for all sorted immune-cell populations. Sorted immune-cell samples labeled by cell-type and study it derives from. BP = BLUEPRINT. e As (a) but for sorted neurons from 4 different cohorts. In each panel we give the R-value (same as PCC) and corresponding correlation test P-value. f Scatterplot of a normal tissue’s relative intrinsic rate (RIR) estimated from taking the median of stemTOC’s mitotic age divided by chronological age and multiplied by 10 (y-axis), against the Vogelstein–Tomasetti intrinsic annual rate of stem-cell division (IR) (x-axis), using the normal-adjacent tissues with such estimates. The Pearson and Spearman Correlation Coefficients (PCC & SCC) are given. g Top: Scatterplot of a normal sample’s mitotic age (estimated with stemTOC) vs the estimated total number of stem-cell divisions (TNSC = IR * Age) expressed in a log2-basis, to better highlight the differences between the low and medium turnover tissues. Two-tailed P-value is from a multivariate linear regression including age as a covariate. Bottom: Violin plot representation of middle panel, with normal-adjacent tissue samples grouped into 5 IR-classes, as shown. Low: Thyroid + Lung, MedLow = Liver + Pancreas + Kidney, Med = Prostate + Breast + Bladder, MedHigh = Esophagus + Oral, High = Colon + Rectum + Stomach. h Barplots compare the PCC and significance level attained by stemTOC shown in (g) to the corresponding values for 6 other mitotic clocks. Mitotic clocks based on CpGs that gain/lose methylation with cell division (hypermethylated/hypomethylated) are indicated. RepliTali results are for the probes restricted to 450k beadarrays.