TOPAS (TOP-down Attachment of Seeds) is an iterative approach which aims at connecting the largest number of seed nodes in a top-down fashion through connectors which guarantee the highest flow of a Random Walk with Restart in a network of functional associations.

• Version 1.0

Step 1: Installation

TOPAS is implemented in R (v4.1), and it was tested in a version-controlled conda environment.

Clone the TOPAS repository and follow the instructions to install Miniconda and then execute the following to generate a conda environment with all you need to run TOPAS:

conda env create -f environment.yml

Step 2: Program Execution

Once you have created a new conda environment, make sure to activate it before running TOPAS.

conda activate topas

You can copy this R snippet into your local computer to produce a disease module as an example. You may want to set the path to match the working directory where you cloned the TOPAS repository.

#!/usr/bin/Rscript

setwd('~/topas') 
source('src/TOPAS.R')

## Load network
network_example = 
  readr::read_tsv(file = 'example/FunCoup5_pfc80.tsv.gz', 
                  col_names = c('V1','V2'), 
                  col_types = 'cc')
## Seed gene set
seeds_example = 
  readr::read_table(file = 'example/adrenal_gland_diseases.txt', 
                    col_names = 'V',
                    col_types = 'c')

module_example = 
  TOPAS(
    network = network_example,
    seeds = seeds_example$V,
    expansion_steps = 2,
    cores = 4
    )

readr::write_tsv(module_example, file = 'example/TOPAS_adrenal_gland_diseases.tsv')

NOTE: TOPAS is only designed to process undirected networks!

Reproduce the benchmark

In order to reproduce all figures in the study, follow the instructions below.

1. Unzip the file benchmarkData.zip and access the folder benchmarkData:

 unzip benchmarkData.zip
 cd benchmarkData

2. Execute the following to generate a conda environment with all you need to execute the notebooks:

conda env create -f environment_benchmark.yml

3. Once you have created a new conda environment, make sure to activate it before executing the notebooks.

conda activate topas_benchmark

4. To execute any notebook from command line, enter the folder dedicated to one specific session of the study and render the notebook called FiguresGenerator.Rmd.

## For example
cd AssessmentOfSRR\&SCR
Rscript -e "rmarkdown::render('FiguresGenerator.Rmd')"

NOTE: All figures are pre-generated and stored in dedicated folders under figures/ and displayed in the html files. However, you are welcome to reproduce the results executing the notebooks.

Contacts

• Davide Buzzao (davide.buzzao@scilifelab.se)
• Erik L.L. Sonnhammer (erik.sonnhammer@scilifelab.se)