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Can we integrate method-specific age-predictive models?: Analysis method-induced differences in detected DNA methylation status

  • Sae Rom Hong
    Affiliations
    Department of Forensic Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50–1 Yonsei-ro, 03722 Seoul, Republic of Korea
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  • Kyoung-Jin Shin
    Correspondence
    Corresponding author.
    Affiliations
    Department of Forensic Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50–1 Yonsei-ro, 03722 Seoul, Republic of Korea
    Search for articles by this author
Published:November 09, 2022DOI:https://doi.org/10.1016/j.fsigen.2022.102805

      Highlights

      • The same amplicons from the same samples allow to reveal the differences dependent on the DNA methylation analysis methods.
      • There were high degrees of positive correlation between single-base extension and massively parallel sequencing results.
      • Despite high correlations between the two methods, detected DNA methylation status was not identical in most markers.
      • Rather than exploiting integrated models, applying method-specific models would achieve higher accuracy in age prediction.

      Abstract

      Forensic research surrounding the use of DNA methylation (DNAm) markers to predict age suggests that accurate prediction of chronological age can be achieved with just several DNAm markers. Several age-prediction models are based on DNAm levels that are detectable by a diverse range of DNAm analysis methods. Among the many DNAm analysis methods, targeted amplicon-based massively parallel sequencing (MPS) and single-base extension (SBE) methods have been widely studied owing to their practicality, including their multiplex capabilities. Since these two DNAm analysis methods share an identical amplification step during their experimental processes, several studies have compared the differences between the methods to construct integrated age-prediction models based on both MPS and SBE data. In this study, we compared the specific differences in DNAm levels between these two commonly exploited analysis methods by analyzing the identical PCR amplicons from the same samples and quantifying the actual bisulfite-converted DNA amount involved in the PCR step. The DNAm levels of five well-studied age-associated markers—CpGs on the ELOVL2, FHL2, KLF14, MIR29B2CHG, and TRIM59 genes—were obtained from blood samples of 250 Koreans using both DNAm analysis methods. The results showed that only ELOVL2 is interchangeable between the MPS and SBE methods, while the rest of the markers showed significant differences in DNAm values. These differences may result in high errors and consequential lowered accuracy in age estimates. Therefore, a DNAm analysis method-specific approach that considers method-induced DNAm differences is recommended to improve the overall accuracy and reliability of age-prediction methods.

      Keywords

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