Improving Single-Cell Transcriptomic Aging Clocks
Enhancing Accuracy and Biological Interpretability
V. Alexan (TU Delft - Electrical Engineering, Mathematics and Computer Science)
Marcel J.T. Reinders – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
I.B. Pronk – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
I.C. den Hond – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
Gerard A. Bouland – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
Kaitai Liang – Graduation committee member (TU Delft - Cyber Security)
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Abstract
Biological aging clocks estimate age from molecular data and provide insights into age-related functional decline. While aging clocks based on bulk transcriptomic data are well-studied, their single-cell counterparts remain limited and underexplored. In this study, we replicate and enhance a recent single-cell RNA-seq aging clock for human immune cells using ElasticNet, improving its performance through refined preprocessing, feature selection, and regularization. We also explore LightGBM to assess nonlinear modeling potential. Our enhanced models reduce prediction error, generalize better across external datasets, and identify biologically relevant genes through SHAP analysis. These findings support the development of accurate, interpretable, cell-type-specific aging clocks using single-cell data.