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. 2022 Mar 1;14:24. doi: 10.1186/s13073-022-01018-w

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© The Author(s) 2022

Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — PanNENs subdivide into two main methylation groups. a Characterization of PanNEN cohort. WHO, World Health Organization; CCP, comprehensive cancer panel. b Unsupervised class discovery using 10,000 (10K) most variable methylation probes. Heatmap displays pairwise consensus values of the samples. c tSNE representation of PanNEN subgroups using 10K most variable probes. d. Heatmap displaying methylation status of 10K variable probes in each of the Groups A, B, and C. Methylation beta value was used to perform hierarchical clustering separately on each subgroup, identifying closely similar samples. Color range blue to red represents methylation beta value, columns indicate samples, and rows methylation probes. e Mean methylation of CpG island probes in PanNEN subgroups. Boxplot represents the distribution of mean methylation, each dot depicts a sample. f GO ontology analysis of 10K most variable probes, representing top 12 terms based on -Log10P-value. g Mean methylation of human Embryonic Stem Cells (hESC) associated hypermethylated and hypomethylated probes in PanNEN subgroups. Boxplot represents the distribution of hypermethylated (red) and hypomethylated (blue) CpG probes of hESC in cohort (left panel), or only in PanNETG3/ PanNEC samples from Group A and B respectively (right panel). Two-sample Wilcoxon test. Boxes show 25th and 75th percentiles and sample median as horizontal line, whiskers show maximum and minimum point