DNA methylation changes across the genome in patients with TET2mt CH and DNMT3Amt CH. (A) Overview of patient cohorts from whom PBMCs were collected and analyzed in this study using DNA methylation (Illumina Methylation EPIC array), single-cell proteogenomics (Tapestri assay), scRNA-seq (10x Genomics), multiome (10x Genomics), and GoTChA modalities. Mutations and VAFs are shown above the figurines. Patient ages and modalities used are shown below the figurines. Sample identifier is shown inside the figurines. (B) Box plot showing the comparison of global DNA methylation between DNMT3Amt and TET2mt CH. There was no significant difference by Wilcoxon signed-rank test (P = .057). (C) Density plot demonstrating DNA methylation differences between TET2mt CH and DNMT3Amt CH, primarily affecting highly methylated CpGs (β > 0.75; Kolmogorov-Smirnov test, P < 2.2 × 10⁻¹⁶). (D) Circos plot showing the number, genomic location, and density of differentially methylated regions between TET2mt CH and DNMT3Amt CH. There was an increased number of hypomethylated sites in DNMT3Amt CH compared with TET2mt CH. (E) Functional annotation of the differentially methylated regions (with Δβ > 10% and P < .010) using the ENCODE Epigenomics Roadmap PBMC reference data. Hypermethylation of Enh and promoters (TssA, TssAFlnk) was more commonly observed in DNMT3Amt CH (compared with TET2mt CH), whereas the hypomethylation observed in DNMT3A CH was predominately found at actively transcribed states (Tx, TxWk). scATAC, single-cell ATAC; TssA, active transcription start site; TssAFlnk, Flanking bivalent transcription start sites.