Precious1GPT: multimodal transformer-based transfer learning for aging clock development and feature importance analysis for aging and age-related disease target discovery.

Journal: Aging
Published Date:

Abstract

Aging is a complex and multifactorial process that increases the risk of various age-related diseases and there are many aging clocks that can accurately predict chronological age, mortality, and health status. These clocks are disconnected and are rarely fit for therapeutic target discovery. In this study, we propose a novel approach to multimodal aging clock we call Precious1GPT utilizing methylation and transcriptomic data for interpretable age prediction and target discovery developed using a transformer-based model and transfer learning for case-control classification. While the accuracy of the multimodal transformer is lower within each individual data type compared to the state of art specialized aging clocks based on methylation or transcriptomic data separately it may have higher practical utility for target discovery. This method provides the ability to discover novel therapeutic targets that hypothetically may be able to reverse or accelerate biological age providing a pathway for therapeutic drug discovery and validation using the aging clock. In addition, we provide a list of promising targets annotated using the PandaOmics industrial target discovery platform.

Authors

  • Anatoly Urban
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Denis Sidorenko
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Diana Zagirova
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Ekaterina Kozlova
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Aleksandr Kalashnikov
    Insilico Medicine, Masdar City, United Arab Emirates.
  • Stefan Pushkov
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Vladimir Naumov
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Viktoria Sarkisova
    Insilico Medicine, Pak Shek Kok, New Territories, Hong Kong.
  • Geoffrey Ho Duen Leung
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Hoi Wing Leung
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Frank W Pun
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Ivan V Ozerov
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Alex Aliper
    Pharma.AI Department , Insilico Medicine, Inc. , Baltimore , Maryland 21218 , United States.
  • Feng Ren
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Alex Zhavoronkov
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.