Here we introduce NetColoc, a tool which evaluates the extent to which two gene sets are related in network space, i.e. the extent to which they are colocalized in a molecular interaction network, and interrogates the underlying biological pathways and processes using multiscale community detection.

This framework may be applied to any number of scenarios in which gene sets have been associated with a phenotype or condition, including rare and common variants within the same disease, genes associated with two comorbid diseases, genetically correlated GWAS phenotypes, GWAS across two different species, or gene expression changes after treatment with two different drugs, to name a few.

NetColoc relies on a dual network propagation approach to identify the region of network space which is significantly proximal to both input gene sets, and as such is highly effective for small to medium input gene sets.

For a quick-start on NetColoc's functionality, please see the example notebooks.

Usage Note: Please follow steps in example notebooks for correct usage of NetColoc. At this time, individual functionalities have not been tested for independent use.

NetColoc requires the following python packages:

• click

• matplotlib

• ndex2

• networkx

• numpy

• seaborn

• tqdm

• mygene >= 3.2.2

• scipy >= 1.5.3

• statsmodels

• gprofiler-official >= 1.0.0

• ipywidgets

• ipycytoscape

• python3 branch of DDOT

  DDOT can be installed one of two ways:

  1. To install DDOT by downloading the zip file of the source tree:

     wget https://github.com/idekerlab/ddot/archive/refs/heads/python3.zip
     unzip python3.zip
     cd ddot-python3
     python setup.py bdist_wheel
     pip install dist/ddot*py3*whl
     

  2. To install DDOT by cloning the repo:

     git clone --branch python3 https://github.com/idekerlab/ddot.git
     cd ddot
     python setup.py bdist_wheel
     pip install dist/ddot*py3*whl
     

  Note

  Due to dependency issue DDOT, will not work with Python 3.10 or later

Additional requirements for full functionality of example notebook:

• cdapsutil >= 0.2.0a1

NetColoc is available on PyPI

pip install netcoloc

• Free software: MIT license

Rosenthal, Sara Brin, Sarah N. Wright, Sophie Liu, Christopher Churas, Daisy Chilin-Fuentes, Chi-Hua Chen, Kathleen M. Fisch, Dexter Pratt, Jason F. Kreisberg, and Trey Ideker. "Mapping the common gene networks that underlie related diseases." Nature protocols (2023): 1-15.

https://www.nature.com/articles/s41596-022-00797-1

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