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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292881PMC
http://dx.doi.org/10.18632/aging.204788DOI Listing

Publication Analysis

Top Keywords

target discovery
20
aging clock
12
transfer learning
8
aging clocks
8
methylation transcriptomic
8
transcriptomic data
8
aging
7
discovery
6
target
5
precious1gpt multimodal
4

Similar Publications

Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion magnetic resonance imaging (MRI) has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain.

View Article and Find Full Text PDF

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.

View Article and Find Full Text PDF

Breaking a barrier: In trans vlsE recombination and genetic manipulation of the native vlsE gene of the Lyme disease pathogen.

PLoS Pathog

January 2025

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.

Host-pathogen interactions represent a dynamic evolutionary process, wherein both hosts and pathogens continuously develop complex mechanisms to outmaneuver each other. Borrelia burgdorferi, the Lyme disease pathogen, has evolved an intricate antigenic variation mechanism to evade the host immune response, enabling its dissemination, persistence, and pathogenicity. Despite the discovery of this mechanism over two decades ago, the precise processes, genetic elements, and proteins involved in this system remain largely unknown.

View Article and Find Full Text PDF

Anti-Mycobacterial Activity of Bacterial Topoisomerase Inhibitors with Dioxygenated Linkers.

ACS Infect Dis

January 2025

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.

Developing new classes of drugs that are active against infections caused by is a priority for treating and managing this deadly disease. Here, we describe screening a small library of 20 DNA gyrase inhibitors and identifying new lead compounds. Three structurally diverse analogues were identified with minimal inhibitory concentrations of 0.

View Article and Find Full Text PDF

Discovery of Novel Small-Molecule Inhibitors Disrupting the MTDH-SND1 Protein-Protein Interaction.

J Med Chem

January 2025

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, and it is a target for the treatment of breast cancer. In this study, we identified and synthesized a series of novel small-molecule inhibitors of MTDH-SND1 PPI. The representative compound showed potent activity against MTDH-SND1 PPI with an IC of 487 ± 99 nM and tight binding to the SND1-purified protein with a value of 279 ± 17 nM.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!