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. 2018 Jan 15;9:222. doi: 10.1038/s41467-017-02595-w

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© The Author(s) 2018

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — AICDA overexpression induces DNA methylation heterogeneity and hypomethylation in VavP-Bcl2+Aicda tumors. a Density plot showing the inter-tumor pairwise methylation distance between ERRBS profiles of VavP-Bcl2 and VavP-Bcl2+Aicda tumors. VavP-Bcl2+Aicda tumors have greater pairwise distance, indicating increased inter-tumor heterogeneity among methylation profiles; two-sided Wilcoxon's signed-rank test. b Density scatterplot showing the relationship between methylation change (x-axis) and change in inter-tumor diversity (y-axis) for all CpGs manifesting >20% combined methylation level difference and/or IQR difference. c–e Scatterplots showing shift in mean methylation values (c), inter-tumor diversity (d), and intra-tumor heterogeneity (e) of AICDA perturbation signature between VavP-Bcl2 and VavP-Bcl2+Aicda. f Bar plot showing the distribution of AICDA-perturbed CpGs relative to the distribution of all represented CpGs; Fisher’s exact test. g Bar plot showing the relative distribution of AICDA-perturbed CpGs within proximity to CpG islands; Fisher’s exact test (*P < 0.05, **P < 0.01, ***P < 0.001)