iTReX: interactive Therapy Response eXploration

Overview

iTReX is an R/Shiny web application for interactive analysis, visualization and exploration of mono- and combination therapy dose response profiling data and drug target interaction network mapping. iTReX features an extended version of the drug sensitivity score (DSS_asym), integrating an advanced five-parameter logistic dose-response curve model and a differential combination drug sensitivity score (dcDSS) for combination therapy profiling.

iTReX provides a complete workflow for analyzing therapy responses through five main functional modules:

i) the Quality Control and Normalization module (QCN-mod)

ii) the Mono-therapy Response Analysis module (MRA-mod)

iii) the Combination therapy Response Analysis module (CRA-mod)

iv) the drug Hits interaction Network mapping module (HitNet-mod)

v) a module for identifying potential sample-specific omics-based biomarkers from the drug target connectivity networks (Omics-mod)

Prerequisites

Regardless of your operating system, you will need at least:

1. An R interpreter (www.r-project.org) – we recommend version 4.1.2 or later.

2. The pandoc document converter (pandoc.org), version 1.12.3 or later.

   <!-- https://github.com/rstudio/rmarkdown/blob/69e6f983/R/render.R#L316-L320 -->

   pandoc is bundled in the free RStudio Desktop (www.rstudio.com).
   (You may need to add the RStudio/bin/pandoc folder to your PATH manually.)

Optional dependencies include the following:

1. To compile packages from source, several developer tools.

   Note that source compilation can often be skipped at prompts such as this:

   Do you want to install from sources the packages which need compilation? (Yes/no/cancel)

2. To run shinytests, the PhantomJS headless browser (phantomjs.org), version 2.1.1.

   PhantomJS can be installed from with R, see "Installation" section below.

On Windows

• Developer tools are bundled in the free Rtools4 (https://cran.r-project.org/bin/windows/Rtools/).

  Don't forget to add them to your PATH environment variable.

On Linux

• On Ubuntu 20.04, you may use

  sudo apt-get install -y cmake git make pandoc perl libcairo2-dev \
      libcurl4-openssl-dev libgit2-dev libglpk-dev libgmp3-dev libicu-dev \
      libpng-dev libssh2-1-dev libssl-dev libxml2-dev zlib1g-dev
  

  to install pandoc and all system requirements. (If unsure, skip this step first.)

• To run shinytests, the following may be required:

  sudo apt-get install -y cmake git gsfonts imagemagick make pandoc perl \
      libcairo2-dev libcurl4-openssl-dev libfontconfig1-dev libfreetype6-dev \
      libgit2-dev libglpk-dev libgmp3-dev libicu-dev libmagick++-dev \
      libpng-dev libssh2-1-dev libssl-dev libxml2-dev zlib1g-dev
  

Installation

iTReX can be installed from the R command prompt:

1. Install the remotes package from CRAN
   (if you have it installed already, simply install again or ensure it is v2.4.2 or later, compare r-lib/remotes#666):

   install.packages("remotes")
   

2. Install iTReX from GitHub:

   remotes::install_github("iTReX-Shiny/iTReX")
   

   After some up to 30 minutes, you will be greeted by

   * DONE (iTReX)
   

3. Start iTReX:

   iTReX::run()
   

Running tests (optional)

1. Install iTReX with optional dependencies:

   remotes::install_github("iTReX-Shiny/iTReX", dependencies = TRUE, force = TRUE)
   

2. Install PhantomJS:

   shinytest::installDependencies()
   

3. Start iTReX tests:

   iTReX::test()
   

   After a few minutes, you might see the following ideal output:

   Loading required package: shiny
   Running all_tabs.R combo_sample_qc.R  [...]
   ==== Comparing all_tabs... No changes.
   ==== Comparing combo_sample_qc... No changes.
   [...]
   

   Slight rendering differences across platforms and package versions are to be expected.