Combining current knowledge on DNA methylation-based age estimation towards the development of a superior forensic DNA intelligence tool

A common epigenetic clock from childhood to old age

“…Quadratic regression models or power transformations have also been applied in cases where the change of the DNA methylation levels with chronological age demonstrates non-linear patterns [30,36]. Recently, novel statistical tools based on machine learning have been introduced [34,37,41,53]. Common to all these models is the fact that the error obtained is unique, independent of the age of the sample donor, and should be applied to whatever predicted age is achieved.…”

“…In recent years, multiple age prediction models have been developed for forensic analysis using a reduced number of CpG sites. These epigenetic clocks were designed targeting multiple forensic tissues: blood [25,26], saliva [27,28], semen [29], teeth [30] and bones [31]; using a variety of technologies: Pyrosequencing [24,32], EpiTYPER [26,33], SNaPshot [27,28] or Massively Parallel Sequencing [34][35][36][37]; and applying different statistical models, including linear regression [25], quantile regression [38], support vector machine [39] or artificial neural networks [40]; as well as covering different age ranges: adults [41] and children [42]. Common to all of them is the use of a reduced number of markers, from 3 to 16 CpG sites.…”

A cautionary note on altered pace of aging in the COVID-19 era

“…90% of the sites on the HM450 are covered). The biological age predictions using Hovarth 2013 and Hannum clocks while employing the EPIC BeadChip dropped certain CpGs (19 and 6, respectively), and this might result in a moderate offset of age-predictions [25] , [58] .…”

“…These conflicting findings may be attributed to the different array platforms used and CpGs sites interrogated as well as their designated capabilities to predict particular outcomes [13] , [53] , [58] , [59] . Testing of data based on HM450 is not completely overlapping with the markers interrogated with the EPIC BeadChip (only ca.…”

“…For example, there are only five CpGs sites that are commonly found in the three epigenetic aging measures: Hannum, PhenoAge, and Horvath DNAm Age measure including: cg05442902 (P2RXL1), cg06493994 (SCGN), cg09809672 (EDARADD), cg19722847 (IPO8), and cg22736354 (NHLRC1) [Levine]. Only EDARADD and NHLRC1 were included in the previously published mimimized CpG forensic models [58] . The forensic Bekaert’s model has two common CpG DNA methylation sites with Hannum DNAm epigentic clock namely CpG6 ELOVL2 and CpG1 EDARADD genes.…”