A5108921606- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Diet and metabolism studies
- Bioinformatics and Genomic Networks
- Immune cells in cancer
- Gut microbiota and health
Cleveland Clinic Lerner College of Medicine
2024
Shifts in the magnitude and nature of gut microbial metabolites have been implicated Alzheimer's disease (AD), but host receptors that sense respond to these are largely unknown. Here, we develop a systems biology framework integrates machine learning multi-omics identify molecular relationships with non-olfactory G-protein-coupled (termed "GPCRome"). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs 335 metabolites. Using genetics-derived Mendelian randomization...
High microglial heterogeneities hinder the development of microglia-targeted treatment for Alzheimer's disease (AD). We integrated 0.7 million single-nuclei RNA-sequencing transcriptomes from human brains using a variational autoencoder. predicted AD-relevant subtype-specific transition networks disease-associated microglia (DAM), tau microglia, and neuroinflammation-like (NIM). prioritized drugs by specifically targeting microglia-specific validated two independent real-world patient...