Journal: Blood Advances
Article Title: Single-cell multiomics reveal divergent effects of DNMT3A- and TET2- mutant clonal hematopoiesis in inflammatory response ∗
doi: 10.1182/bloodadvances.2024014467
Figure Lengend Snippet: DNA methylation changes across the genome in patients with TET2 mt CH and DNMT3A mt 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 DNMT3A mt and TET2 mt CH. There was no significant difference by Wilcoxon signed-rank test ( P = .057). (C) Density plot demonstrating DNA methylation differences between TET2 mt CH and DNMT3A mt 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 TET2 mt CH and DNMT3A mt CH. There was an increased number of hypomethylated sites in DNMT3A mt CH compared with TET2 mt 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 DNMT3A mt CH (compared with TET2 mt 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.
Article Snippet: We then annotated the differentially methylated regions using the ENCODE Epigenomics Roadmap reference data.
Techniques: DNA Methylation Assay, Methylation, Comparison, Functional Assay