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iTReX: Interactive exploration of mono- and combination therapy dose response profiling data

Dina ElHarouni1, Yannick Berker2, Heike Peterziel2

  • 1Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Pharmacological Research
|December 1, 2021
PubMed

Insights

iTReX is a new R application for analyzing tumor cell drug sensitivity and resistance. It helps identify potential biomarkers and druggable targets for precision oncology by analyzing drug response data.

Area of Science:

  • Computational Biology
  • Pharmacology
  • Bioinformatics

Background:

  • High-throughput screening methods are crucial for assessing tumor cell drug sensitivity and resistance.
  • These methods aid in developing predictive models for treatment response and inform precision oncology decisions.
  • Existing analysis methods for drug efficacy often have limitations in curve fitting and combination therapy assessment.

Purpose of the Study:

  • To introduce iTReX, a user-friendly Shiny/R application for analyzing mono- and combination drug therapy responses.
  • To provide advanced dose-response curve modeling and differential drug sensitivity score (DSS) for combination profiling.
  • To integrate modules for visualizing drug target interaction networks and matching omics data for biomarker discovery.

Main Methods:

  • Development of an interactive Shiny/R application named iTReX.
  • Implementation of an extended drug sensitivity score (DSS) using a five-parameter dose-response model.
  • Inclusion of modules for drug target interaction network visualization and omics data integration.

Main Results:

  • iTReX enables comprehensive analysis of various drug response readouts and treatment strategies.
  • The application successfully validated a cost-effective drug combination screening approach.
  • iTReX demonstrated its capability in identifying sample-specific biomarkers through drug target interaction networks.

Conclusions:

  • iTReX offers a versatile platform for analyzing drug sensitivity and combination therapies in oncology.
  • The application facilitates the identification of potential druggable targets and predictive biomarkers.
  • iTReX supports precision oncology by integrating drug response data with omics features and network analysis.
Keywords:
Asymmetric sensitivity scoringDifferential combination sensitivity scoringDrug target networksInteractive drug screen analysisPersonalized medicineTherapy response profiling and exploration

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