Biologically informed deep learning for explainable epigenetic clocks

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Ageing is often characterised by progressive accumulation of damage, and it is one of the most important risk factors for chronic disease development. Epigenetic mechanisms including DNA methylation could functionally contribute to organismal aging, however the key functions and biological processes may govern ageing are still not understood. Although age predictors called epigenetic clocks can accurately estimate the biological age of an individual based on cellular DNA methylation, their models have limited ability to explain the prediction algorithm behind and underlying key biological processes controlling ageing. Here we present XAI-AGE, a biologically informed, explainable deep neural network model for accurate biological age prediction across multiple tissue types. We show that XAI-AGE outperforms the first-generation age predictors and achieves similar results to deep learning-based models, while opening up the possibility to infer biologically meaningful insights of the activity of pathways and other abstract biological processes directly from the model.

OriginalsprogEngelsk
Artikelnummer1306
TidsskriftScientific Reports
Vol/bind14
Antal sider10
ISSN2045-2322
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Supported by the the European Union project RRF-2.3.1-21-2022-00004 within the framework of the MILAB Artificial Intelligence National Laboratory. G.P. received funding partly from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101021607 and from the National Research, Development and Innovation Office under grant no. K128780. S.S. received funding from National Research Development and Innovation Office Hungary, under grant no. FK142835.

Publisher Copyright:
© 2024, The Author(s).

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