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Network-based drug repurposing for psychiatric disorders using single-cell genomics.

Chirag Gupta1, Noah Cohen Kalafut2, Declan Clarke3

  • 1Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53076, USA.

Cell Genomics
|September 19, 2025
PubMed
Summary
This summary is machine-generated.

This study integrates single-cell genomics and gene networks to find new drug targets for neuropsychiatric disorders like schizophrenia and autism. It identifies potential medicines that could reverse disease-related gene expression changes in specific brain cells.

Keywords:
cell-type-disorder genesdrug repurposingpsychiatric disorderssingle-cell network medicine

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Area of Science:

  • Neuroscience
  • Genomics
  • Pharmacology

Background:

  • Neuropsychiatric disorders lack effective treatments due to poor understanding of cellular and molecular mechanisms.
  • Existing treatments are limited by incomplete knowledge of disease underpinnings.

Purpose of the Study:

  • To identify druggable targets and repurpose drugs for neuropsychiatric disorders using single-cell genomics.
  • To create a cell-type-specific network medicine resource for advancing treatment options.

Main Methods:

  • Integrated population-scale single-cell genomics data from schizophrenia, bipolar disorder, and autism.
  • Analyzed 23 cell-type-level gene regulatory networks.
  • Applied graph neural networks for risk gene prioritization and network-based drug repurposing.

Main Results:

  • Identified co-regulated modules and potential druggable transcription factors linked to neuropsychiatric risk genes.
  • Prioritized novel risk genes and identified 220 drug molecules for cell-type-specific targeting.
  • Found evidence for 37 drugs reversing disorder-associated transcriptional phenotypes.
  • Discovered 335 drug-cell quantitative trait loci (eQTLs) impacting drug target expression.

Conclusions:

  • The study provides a valuable single-cell network medicine resource.
  • Offers potential mechanistic insights for developing novel therapeutic strategies for neuropsychiatric disorders.
  • Highlights the importance of cell-type-specific genetic variations in drug response.