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PhosphoNetworks Manuscript Code

Package Install

This repository contains the code and notebooks that accompany the manuscript:

Garrido-Rodriguez et al., “Unexplored Signaling Pathways: Escaping the Streetlight Effect with Phosphoproteomics and Kinase–Substrate Interactions” (2025)

The phosphonetworks Python module provides all functions required to reproduce the analyses and figures in the paper.
It also includes convenient wrappers for kinase activity estimation and kinase–kinase network inference using the same methods described in the manuscript.


Installation

Clone the repository and install the package with pip in an environment with Python 3.10:

pip install .

Additional dependencies are required for specific analyses and visualizations:

1. Gurobi

Gurobi is used to solve the Rooted Prize-Collecting Steiner Tree problem described in the manuscript.
Academic licenses are available free of charge.
Request a license at: https://www.gurobi.com/

2. Graphviz

Graphviz is needed to generate network plots.
Download and install it from: https://graphviz.org/download/

3. MMSeqs

MMSeqs is used to compute the kinase-kinase sequence similarity scores. Download and install it from: https://mmseqs.com/


Notebooks

Two Jupyter notebooks are provided:

  1. Paper pipeline – Downloads the manuscript’s data from Zenodo and reproduces all analyses and figures.
    Open the notebook

  2. Analysis tutorial – Demonstrates how to estimate kinase activity using different kinase–substrate networks from the paper and how to infer a kinase–kinase signaling network.
    Open the notebook

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