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.

   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.