Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.854797
Keywords
epigenetic; biomarker; hallmarks; DNA methylation; aging; blood counts; methods; IVDD
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Recent advances in sequencing technologies have provided opportunities for the development of epigenetic biomarkers. However, only a few of them have been successfully translated into clinical practice, mostly in oncology. When designing epigenetic biomarkers, factors such as the identification of the best genomic regions, pre-analytical processing, accuracy of DNA methylation measurements, identification of confounding parameters, accreditation as a diagnostic procedure, standardized data analysis, turnaround time, and costs and customer requirements should be considered.
Recent advances in sequencing technologies provide unprecedented opportunities for epigenetic biomarker development. Particularly the DNA methylation pattern-which is modified at specific sites in the genome during cellular differentiation, aging, and disease-holds high hopes for a wide variety of diagnostic applications. While many epigenetic biomarkers have been described, only very few of them have so far been successfully translated into clinical practice and almost exclusively in the field of oncology. This discrepancy might be attributed to the different demands of either publishing a new finding or establishing a standardized and approved diagnostic procedure. This is exemplified for epigenetic leukocyte counts and epigenetic age-predictions. To ease later clinical translation, the following hallmarks should already be taken into consideration when designing epigenetic biomarkers: 1) Identification of best genomic regions, 2) pre-analytical processing, 3) accuracy of DNA methylation measurements, 4) identification of confounding parameters, 5) accreditation as diagnostic procedure, 6) standardized data analysis, 7) turnaround time, and 8) costs and customer requirements. While the initial selection of relevant genomic regions is usually performed on genome wide DNA methylation profiles, it might be advantageous to subsequently establish targeted assays that focus on specific genomic regions. Development of an epigenetic biomarker for clinical application is a long and cumbersome process that is only initiated with the identification of an epigenetic signature.
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