Fig. 2: EPI-Clone reliably identifies clones from DNA methylation data only.
From: Clonal tracing with somatic epimutations reveals dynamics of blood ageing
a, Schematic overview of EPI-Clone. See the main text for details. Exp, expression. b, UMAP of DNA methylation computed on static CpGs only for experiment M.1, which highlights clonal identity as defined by LARRY barcodes. Only cells carrying a LARRY barcode are shown and cells with a relative clone size (rel. size; defined using LARRY) less than 0.25% are shown in grey. c, Same UMAP as in b, but highlighting the cell states as defined in Fig. 1c. d, UMAP highlighting cells that were selected as part of expanded clones based on local density in PCA space. e, Receiver-operating characteristics curve visualizing the performance of classifying cells into expanded and non-expanded clones based on local density in PCA space spanned by the static CpGs. LARRY clone size was used as the ground truth, whereby clone sizes larger than 0.25% were considered expanded. TPR, true positive rate; FPR, false positive rate. f, Heatmap depicting the overlap between LARRY barcode and methylation-based clonal clusters identified by EPI-Clone. The row labelled with an asterisk contains all LARRY clones with a clone size less than 0.25%. g, Schematic of experiment M.5: LARRY mature immune cell experiment. h, UMAP of DNA methylation for cells from expanded clones in experiment M.5. Cells are coloured by LARRY barcode. The static CpGs identified from experiment M.1 were used. i, Same UMAP representation as in h, but highlighting the cell-state annotation as defined in Supplementary Fig. 4. Of note, most of the clones identified using EPI-Clone were specific for T cells, B cells or myeloid cells, in line with the result from LARRY (Supplementary Fig. 4d). j, ARI values between the ground-truth clonal label (LARRY) and the clones identified by EPI-Clone stratified by cell type.
