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@ARTICLE{Becker:1030922,
      author       = {Becker, J. and Bühren, V. and Schmelzer, L. and Reckert,
                      A. and Eickhoff, S. B. and Ritz, S. and Naue, J.},
      title        = {{M}olecular age prediction using skull bone samples from
                      individuals with and without signs of decomposition: a
                      multivariate approach combining analysis of
                      posttranslational protein modifications and {DNA}
                      methylation},
      journal      = {International journal of legal medicine},
      volume       = {139},
      issn         = {0367-0031},
      address      = {Getzville, NY},
      publisher    = {HeinOnline},
      reportid     = {FZJ-2024-05515},
      pages        = {157-174},
      year         = {2025},
      abstract     = {The prediction of the chronological age of a deceased
                      individual at time of death can provide important
                      information in case of unidentified bodies. The
                      methodological possibilities in these cases depend on the
                      availability of tissues, whereby bones are preserved for a
                      long time due to their mineralization under normal
                      environmental conditions. Age-dependent changes in DNA
                      methylation (DNAm) as well as the accumulation of
                      pentosidine (Pen) and D-aspartic acid (D-Asp) could be
                      useful molecular markers for age prediction. A combination
                      of such molecular clocks into one age prediction model seems
                      favorable to minimize inter- and intra-individual variation.
                      We therefore developed (I) age prediction models based on
                      the three molecular clocks, (II) examined the improvement of
                      age prediction by combination, and (III) investigated if
                      samples with signs of decomposition can also be examined
                      using these three molecular clocks. Skull bone from deceased
                      individuals was collected to obtain a training dataset
                      (n = 86), and two independent test sets (without signs
                      of decomposition: n = 44, with signs of decomposition:
                      n = 48). DNAm of 6 CpG sites in ELOVL2, KLF14, PDE4C,
                      RPA2, TRIM59 and ZYG11A was analyzed using massive parallel
                      sequencing (MPS). The D-Asp and Pen contents were analyzed
                      by high performance liquid chromatography (HPLC). Age
                      prediction models based on ridge regression were developed
                      resulting in mean absolute errors (MAEs)/root mean square
                      errors (RMSE) of 5.5years /6.6 years (DNAm), 7.7 years /9.3
                      years (Pen) and 11.7 years /14.6 years (D-Asp) in the test
                      set. Unsurprisingly, a general lower accuracy for the DNAm,
                      D-Asp, and Pen models was observed in samples from
                      decomposed bodies (MAE: 7.4–11.8 years, RMSE: 10.4–15.4
                      years). This reduced accuracy could be caused by multiple
                      factors with different impact on each molecular clock. To
                      acknowledge general changes due to decomposition, a pilot
                      model for a possible age prediction based on the decomposed
                      samples as training set improved the accuracy evaluated by
                      leave-one-out-cross validation (MAE: 6.6–12 years, RMSE:
                      8.1–15.9 years). The combination of all three molecular
                      age clocks did reveal comparable MAE and RMSE results to the
                      pure analysis of the DNA methylation for the test set
                      without signs of decomposition. However, an improvement by
                      the combination of all three clocks was possible for the
                      decomposed samples, reducing especially the deviation in
                      case of outliers in samples with very high decomposition and
                      low DNA content. The results demonstrate the general
                      potential in a combined analysis of different molecular
                      clocks in specific cases.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5254 - Neuroscientific Data Analytics and AI (POF4-525) /
                      5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5254 / G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {39256256},
      UT           = {WOS:001309228800002},
      doi          = {10.1007/s00414-024-03314-z},
      url          = {https://juser.fz-juelich.de/record/1030922},
}