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Related Experiment Video

Updated: Jan 21, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
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A genome-wide positioning systems network algorithm for in silico drug repurposing.

Feixiong Cheng1,2,3, Weiqiang Lu4, Chuang Liu5

  • 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

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|August 4, 2019
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This study introduces GPSnet, an algorithm for drug repurposing using patient DNA/RNA data to target disease modules. It identifies approved drugs, like ouabain, for new cancer treatments.

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Area of Science:

  • Genomics
  • Systems Biology
  • Pharmacology

Background:

  • DNA/RNA sequencing advances enable rapid target identification and drug repurposing for complex diseases.
  • Precise targeting of individualized disease modules is crucial for effective therapeutic strategies.

Purpose of the Study:

  • To develop a Genome-wide Positioning Systems network (GPSnet) algorithm for drug repurposing.
  • To target disease modules identified from individual patient sequencing data within the human protein-protein interactome network.

Main Methods:

  • Utilized whole-exome sequencing and transcriptome profiles from ~5,000 cancer patients (The Cancer Genome Atlas).
  • Applied the GPSnet algorithm to map patient-specific profiles onto the human protein-protein interactome network.
  • Experimentally validated drug efficacy and identified novel therapeutic pathways.

Main Results:

  • GPSnet successfully predicted drug responses and prioritized new indications for 140 approved drugs across 15 cancer types.
  • Identified ouabain, a cardiac drug, as having potential antitumor activity in lung adenocarcinoma.
  • Discovered that ouabain targets a HIF1α/LEO1-mediated cell metabolism pathway.

Conclusions:

  • GPSnet provides a network-based, in silico framework for effective drug repurposing.
  • This approach enhances therapeutic selection by leveraging individual patient genomic and transcriptomic data.
  • Experimental validation confirms the potential of GPSnet in identifying novel drug indications.