Kinase activity inference from phosphosproteomics data based on substrate sequence specificity

Current version: 0.6.0

Research paper: https://doi.org/10.1101/2024.03.22.586304

Overview

PhosX infers differential kinase activities from phosphoproteomics data without requiring any prior knowledge database of kinase-phosphosite associations. PhosX assigns the detected phosphopeptides to potential upstream kinases based on experimentally determined substrate sequence specificities, and it tests the enrichment of a kinase's potential substrates in the extremes of a ranked list of phosphopeptides using a Kolmogorov-Smirnov-like statistic. A p value for this statistic is extracted empirically by random permutations of the phosphosite ranks.

Installation

From PyPI

pip install phosx

From source (requires Poetry)

poetry build
pip install dist/*.whl

Usage

phosx [-h] [-p PSSM] [-q PSSM_QUANTILES] [-n N_PERMUTATIONS] [-k N_TOP_KINASES] [-m MIN_N_HITS] [-c N_PROC] [--plot-figures] [-d OUTPUT_DIR] [-o OUTPUT_PATH] [-v] seqrnk

positional arguments:
  seqrnk                Path to the seqrnk file.

options:
  -h, --help            show this help message and exit
  -p PSSM, --pssm PSSM  Path to the h5 file storing custom PSSMs; defaults to built-in PSSMs
  -q PSSM_QUANTILES, --pssm-quantiles PSSM_QUANTILES
                        Path to the h5 file storing custom PSSM score quantile distributions under the key 'pssm_scores'; defaults to built-in PSSM scores quantiles
  -n N_PERMUTATIONS, --n-permutations N_PERMUTATIONS
                        Number of random permutations; default: 1000
  -k N_TOP_KINASES, --n-top-kinases N_TOP_KINASES
                        Number of top-scoring kinases potentially associatiated to a given phosphosite; default: 8
  -m MIN_N_HITS, --min-n-hits MIN_N_HITS
                        Minimum number of phosphosites associated with a kinase for the kinase to be considered in the analysis; default: 4
  -c N_PROC, --n-proc N_PROC
                        Number of cores used for multithreading; default: 1
  --plot-figures        Save figures in pdf format; see also --output_dir
  -d OUTPUT_DIR, --output-dir OUTPUT_DIR
                        Output files directory; only relevant if used with --plot_figures; defaults to 'phosx_output/'
  -o OUTPUT_PATH, --output-path OUTPUT_PATH
                        Main output table; if not specified it will be printed in STDOUT
  -v, --version         Print package version and exit

Minimal example to run PhosX with default parameters on an example dataset, using up to 8 cores, and redirecting the output table to kinase_activities.tsv:

phosx -c 8 tests/seqrnk/koksal2018_log2.fold.change.8min.seqrnk > kinase_activities.tsv

Cite

BibTeX:

@article{Lussana2024,
  title = {PhosX: data-driven kinase activity inference from phosphoproteomics experiments},
  url = {http://dx.doi.org/10.1101/2024.03.22.586304},
  DOI = {10.1101/2024.03.22.586304},
  publisher = {Cold Spring Harbor Laboratory},
  author = {Lussana,  Alessandro and Petsalaki,  Evangelia},
  year = {2024},
  month = mar 
}