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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.

Ischemic stroke (IS) is the majority of strokes which remain the second leading cause of deaths in the last two decades. Circulating microRNAs (miRNAs) have been suggested as potential diagnostic and therapeutic tools for IS by previous studies analyzing their differential expression. However, inconclusive and controversial conclusions of these results have to be addressed. In this study, comprehensive analysis and real-world validation were performed to assess the associations between circulating miRNAs and IS. 29 studies with 112 miRNAs were extracted after manual selection and filtering, 12 differentially expressed miRNAs were obtained from our results of meta-analysis. These miRNAs were evaluated in 20 IS patients, compared to 20 healthy subjects. 4 miRNAs (hsa-let-7e-5p, hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-185-5p) exhibited the significant expression level in IS patient plasma samples. Pathway and biological process enrichment analysis for the target genes of the 4 validated miRNAs identified cellular senescence and neuroinflammation as key post-IS response pathways. The results of our analyses closely correlated with the pathogenesis and implicated pathways observed in IS subjects suggested by the literature, which may provide aid in the development of circulating diagnostic or therapeutic targets for IS patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)