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PharmGWAS: a GWAS-based knowledgebase for drug repurposing.

Hongen Kang1,2, Siyu Pan1,2, Shiqi Lin1,2

  • 1CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.

Nucleic Acids Research
|October 13, 2023
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Summary
This summary is machine-generated.

PharmGWAS integrates genome-wide association studies (GWAS) data with drug perturbation signatures to identify novel drug repurposing candidates. This knowledgebase links diseases to potential small-molecule compounds, aiding drug discovery and therapy exploration.

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Area of Science:

  • Pharmacology
  • Genetics
  • Bioinformatics

Background:

  • Genetics insights are increasingly vital for drug repurposing, with two-thirds of FDA-approved drugs in 2021 having genetic support.
  • Genome-wide association studies (GWAS) datasets offer significant opportunities for genetics-driven drug discovery.

Purpose of the Study:

  • To develop PharmGWAS, a comprehensive knowledgebase for identifying candidate drugs by integrating GWAS data.
  • To establish novel connections between diseases and small-molecule compounds using a reverse relationship between genetic and drug signatures.

Main Methods:

  • Collected and processed 1929 GWAS datasets and 724,485 drug perturbation signatures for 33,609 compounds.
  • Implemented six distinct connectivity methods to ensure reliable predictions for reverse connections.
  • Integrated genetic expression signatures with drug-induced signatures to identify disease-drug pairs.

Main Results:

  • PharmGWAS contains 740,227 genetically-informed disease-drug pairs.
  • The knowledgebase provides a valuable catalog for drug repurposing based on genetic evidence.
  • A user-friendly web interface facilitates exploration of drug discovery and therapy options.

Conclusions:

  • PharmGWAS is a valuable resource for identifying novel drug candidates and exploring drug combination therapies.
  • The platform can aid in understanding drug resistance and side effects.
  • PharmGWAS supports genetics-based drug discovery and repurposing strategies.