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Fig. 2 | Genome Biology

Fig. 2

From: DNA methylation aging clocks: challenges and recommendations

Fig. 2

All clock probes are strongly biased to reside within active functional loci. This is due to their construction from promoter-focused arrays. Overlap of CpGs from four DNA methylation clocks with the six Core Encode Combined Chromatin Segmentation tracks [130] from ENCODE Analysis Data at UCSC. a Horvath clock [24]. b Hannum et al. clock [23]. c PhenoAge clock [43]. d epiTOC clock [31]. Location is assessed for overlap with the seven functional categories: PF (promoter flanking—light red), TSS (transcription start site and promoter region—red), CTCF (blue), WE (weak enhancer—yellow), E (enhancer—gold), T (transcribed region—green), and R (repressed—grey), from any of the six Core Encode cell types (Gm12878, H1hesc, Helas3, Hepg2, Huvec, K562). This percentage overlap is shown on the y-axis and is compared with the percentage overlap for all ~28 × 106 CpGs in the human genome on the x-axis. Calculated via bedtools [131]. The size of the circle is proportional to the entire genome space for each functional category (~10(genome size proportion)). e-h Direct overlap comparison for four DNA methylation clocks (Horvath clock, Hannum et al. clock, PhenoAge clock, epiTOC clock) as well as Illumina array CpGs (27k, 450k, EPIC) and all genomic CpGs (far right bar) with: e the Combined Segmentation track for blood-derived tissue (GM12878) [130]. Functional segments are delineated as PF (promoter flanking), TSS (transcription start site and promoter region), CTCF, WE (weak enhancer), E (enhancer), T (transcribed region), and R (repressed). NC, not covered CpGs in this Combined Segmentation overlap; f Gencode [132] Exon and Transcripts; g UCSC [133]-defined CpG islands and shore regions (+/−2 kb); h Major repeat classes (UCSC RepeatMasker [133]), including DNA repeat elements (DNA_repeats), long interspersed nuclear elements (LINE), low complexity repeats and other rare repeat classes, long terminal repeat elements (LTR), simple repeats (microsatellites aka short tandem repeats), and short interspersed nuclear elements (SINE), of which ~63% are Alu elements

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