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. 2022 Oct 29;13:6467. doi: 10.1038/s41467-022-34012-2

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© The Author(s) 2022

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 — A Volcano plot of differentially methylated regions (DMRs) was identified comparing metastatic and localized prostate cancer. A total of 2493 and 19,048 hypo and hyper DMRs were identified, respectively. Pearson correlation between the mean methylation levels of hyper (B) and hypo (C) DMRs and %ctDNA. P value was calculated using t test. Blue line represents a fitted linear model of the data and shading around the fitted line represents 0.95 CI. Genomic distribution of hyper- (D) and hypo- (E) DMRs. F Contingency table showing the distribution of repeat and the hypo-DMRs. Two-sided fisher’s exact test was used to calculate p value and odds ratio (OR). G Frequency of repeat types overlapped with downregulated peaks. H Differentially methylated peaks located within the 1 Mb regions flanking the centromere. CPC Canadian Prostate Cancer Genome Network cohort. I Example showing signal distribution around the pericentromeric region in chromosome 2. The Y axis showed the normalized signal per million reads (SPMR) from MACS (v2.2.5). Mean methylation levels for differential peaks shown in H for cfMeDIP-seq (J) and WGBS (K) data. Box plots represent median values and 0.25 and 0.75 quantiles. Whiskers represent 1.5× IQR. X = 30, and 67 independent experiments for the CPC and VPC cohorts, respectively in J. X = 194, 194, and 100 independent experiments for the Benign, Primary, and Mets groups, respectively, in K. Source data for F2B-C and 2J-K are provided as a Source Data file.