PS4DR (Pathway Signatures for Drug Repositioning)

This package comprises a modular workflow designed to identify drug repositioning candidates using multi-omics data sets. A schematic figure of the workflow is presented below. The R scripts necessary to run the MSDRP pipeline are located in the R directory.

Figure 1. Design of the MSDRP workflow. Differentially expressed genes/proteins (i.e., DEG/DEP) from disease and drug perturbed profiles are passed as input together with GWAS data. Once the data is correctly formatted, users can define a custom pipeline, or series of steps in the workflow that will then be applied to the datasets. The steps performed in this pipeline constitute the optional portion of the workflow and involve filtering the -omics features coming from the dataset in order to reduce dimensionality by exclusively analyzing genes that have been associated with GWAS studies. Next, a previously selected pathway enrichment method is applied to DEG/DEP datasets deriving from both the disease and drug perturbed profiles to evaluate the direction of dysregulation for each affected pathway in each of these contexts. Finally, the workflow prioritizes drugs by finding the drugs that are predicted to invert the pathway signatures observed in the pathophysiology context.

Citation

If you use PS4DR in your work, please consider citing our preprint:

[1]	Emon, M. A., Domingo-Fernández, D., Hoyt, T. C., Hofmann-Apitius, M. (2020). PS4DR: a multimodal workflow for identification and prioritization of drugs based on pathway signatures. BMC Bioinformatics, 21:231.

Installation

If devtools is not installed, do:

$ R -e 'install.packages("devtools", repos="http://cran.us.r-project.org")'

This library can be installed directly from GitHub using the following instructions adapted from R Package primer:

$ R -e 'library(devtools); install_github("ps4dr/ps4dr")'

Alternatively, ps4dr can be cloned then installed from the source with:

$ R -e 'install.packages(c("cowplot", "BiocManager", "data.table", "doParallel", "dplyr", "ggplot2", "gridExtra", "Hmisc", "httr", "jsonlite", "pROC", "purrr", "qqplotr","RColorBrewer", "RecordLinkage", "stringr", "tools", "tidyr", "VennDiagram"))'
$ R -e 'BiocManager::install(c("BiocParallel", "biomaRt", "graphite", "org.Hs.eg.db", "SPIA"))'

Then

$ git clone https://github.com/ps4dr/ps4dr.git
$ R -e 'library(devtools); install("ps4dr")'

Reproduction

To run the entire pipeline:

$ sh ps4dr.sh

Alternatively, see the instructions to:

1. Run all pre-processing scripts using the instructions at https://github.com/ps4dr/ps4dr/tree/master/R/preprocessing
2. Run all analysis scripts using the instructions at https://github.com/ps4dr/ps4dr/tree/master/R/analysis

How to Modify the Workflow

Notes how to change parts of the workflow:

1. Selecting different gene sets (i.e., "gene set intersection" part in the figure)
2. Modifying the Pathway enrichment Analysis method (i.e., GSEA instead of SPIA)

Disclaimer

PS4DR is a scientific software that has been developed in an academic capacity, and thus comes with no warranty or guarantee of maintenance, support, or back-up of data.