Abstract
Dementia, including Alzheimer's, frontotemporal, vascular, & Lewy body dementia, is characterized by neuron loss & cognitive decline, yet effective treatments are lacking. Emerging data suggest that deviations in cell fate trajectories contribute to disease progression. By integrating these trajectories across different dementias, we aim to uncover shared pathways & disease-specific mechanisms to inform targeted treatments. Using scRNA-seq & scATAC-seq data, we will apply advanced methods like manifold alignment to model & integrate cell fate trajectories, identify critical bifurcation points, & pinpoint therapeutic targets. Our approach seeks to: Develop a computational method to distinguish cell fate trajectories across dementias, Identify disease-specific bifurcation points, Uncover the molecular mechanisms driving these changes, & Identify potential therapeutic targets. We hypothesize that cell fate trajectories can be mapped onto hyperbolic spaces, revealing similarities & differences between diseases. Interpretable techniques, such as integrated gradients, will help us link molecular insights to therapeutic targets, offering new opportunities for early intervention. This project aims to provide a comprehensive framework for understanding cell fate deviations in dementia, identifying shared & unique molecular mechanisms across dementias. By targeting key events along these trajectories, our work could enable earlier diagnosis, transforming dementia research & treatment.
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