Insilico Medicine's transformer-based aging clock provides insights into aging, disease, and new therapeutic targets

June 15th, 2023
The multimodal transformer-based aging clock is capable of processing diverse data sets and providing insights into biomarkers for aging, mapping them to genes relevant to both aging and disease, and discovering new therapeutic targets. Credit: Insilico Medicine

Clinical stage generative artificial intelligence (AI)-driven drug discovery company Insilico Medicine ("Insilico") has announced a new multimodal transformer-based aging clock that is capable of processing diverse data sets and providing insights into biomarkers for aging, mapping them to genes relevant to both aging and disease, and discovering new therapeutic targets designed to slow or reverse both aging and aging-related diseases. The company calls the aging clock Precious1GPT, in a nod to the powerful "One Ring" in Lord of the Rings. The findings were published in the June 13 issue of the journal Aging.

Insilico has been at the forefront of both generative AI and aging research, and began publishing studies on biomarkers of aging using advanced bioinformatics in 2014. Later, the company trained deep neural networks (DNNs) on human "multi-omics" longitudinal data and retrained them on diseases to develop its end-to-end Pharma.AI platform for target discovery, drug design, and clinical trial prediction.

"We have long used DNNs to better understand human disease and aging biology," says Alex Zhavoronkov, Ph.D., founder and CEO of Insilico Medicine and the study's corresponding author. "Now, with great advancements in generative AI capabilities, including AI-based transformers, we are able to further accelerate this process to make an aging clock that can not only identify where aging and disease intersect, but connect that information to actionable therapeutic targets."

Transformer-based neural networks have only recently become available. First, scientists pretrain algorithms on unlabeled data, and then they further refine those algorithms with smaller sets of labeled data. Multimodal transformer models can process diverse data types, including genomic, proteomic, microscopy, computational chemistry, and clinical imaging data.

In the study, a team of researchers used a method called Precious1GPT that involves a multimodal transformer-based regressor trained on diverse data—including RNA sequencing and epigenetics methylation—for age prediction, and identified genes most relevant to both aging and diseases. The multimodal transformer was able to predict biological age and distinguish between disease and control samples. Scientists then fed the gene lists into Insilico's AI target identification engine, PandaOmics, and discovered targets highly associated with both aging and four age-related diseases—idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, Parkinson's disease, and heart failure. Both APLNR and IL23R emerged as potential targets for the delay and treatment of age-related diseases.

"Applying generative biology to aging and disease using a transformer-based approach gives us new insight into how these complex biological processes interact, and clues as to how we can slow or reverse their progress through new therapeutic approaches," says Frank Pun, Ph.D., Head of Insilico's Hong Kong Office and co-author of the study.

The findings will be presented at the upcoming Aging Research and Drug Discovery conference in Copenhagen, now in its 10th year, the most significant gathering of academic and industry leaders focused on aging and longevity research, commercialization, and investment.

Insilico scientists plan to further develop this approach by applying it to larger, proprietary disease-specific datasets and validating their findings through lab experiments. Ultimately, they hope to use this technique to better understand the molecular mechanisms of aging and develop new interventions for both aging and aging-related diseases.

About Insilico Medicine

Insilico Medicine, a clinical stage end-to-end generative artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases.

Website: www.insilico.com

More information:
Anatoly Urban et al, Precious1GPT: multimodal transformer-based transfer learning for aging clock development and feature importance analysis for aging and age-related disease target discovery, Aging (2023). DOI: 10.18632/aging.204788

Provided by InSilico Medicine