protiler-mut 0.1.0

Pipeline for comprehensive analysis of tiling mutagenesis data

ProTiler-Mut

Introduction of ProTiler-Mut

Hi, this is ProTiler-Mut, a computational pipeline designed for comprehensive analysis of tiling mutagenesis screen data

I have three major functions: 1). Clustering and Categorization of functional mutations from tiling mutagenesis screens
                              2). "3D-RRA" module for robust identification of functional substructures from identified mutation clusters
                              3). PPI-mapping for specific mutation or substructure to identify mutaiton-associated PPIs


Hope you enjoy playing with me ^o^!
                                 
Any questions or bugs, please contact [e-mail] or [e-mail]

Installation

If Anaconda (or miniconda) is not installed with Python 3, it is highly recommended to download and install Python3 Anaconda from here: https://www.anaconda.com/download/

Dependencies

Python Packages: Following are the specific versions used when developing the tool, other versions should also be OK, if it is not,please install the corresponding version instead

 biopython==1.79, matplotlib==3.5.3, mygene==3.2.2, numpy==1.21.6, 
 pandas==1.3.5, Requests==2.32.3, rich==14.0.0, scikit_learn==0.20.0, scipy==1.7.3, 
 seaborn==0.13.2, setuptools==68.0.0, statsmodels==0.13.5, umap_learn==0.5.3

Pymol is required for ProTiler-Mut, install it using following command:

conda install -c conda-forge pymol-open-source

On macOS, you need this command in addition:

pip install PyQt5

There are three ways to install ProTiler-Mut

Install ProTiler-Mut through pip

pip install ProTiler-Mut

OR you can install ProTiler-Mut through git clone

git clone https://github.com/MDhewei/ProTiler-Mut.git
cd ProTiler-Mut
pip install -r requirements.txt .

OR you can install ProTiler-Mut through Docker

With Docker no installation is required, the only dependence is Docker itself. Users will completely get rid of all the installation and configuration issues. Docker will do all the dirty work for you!

Docker can be downloaded freely from here: https://store.docker.com/search?offering=community&type=edition

To get an image of ProTiler-Mut, simply execute the following command:

$ docker pull MDhewei/ProTiler-Mut

How to use ProTiler-Mut

1. ProTiler-Mut cluster: Perform the clustering and categorization of functional mutations

   usage: protiler-mut.py cluster [-h] -i INPUTFILE -g GENE_ID -s SAMPLES -c CONTROL [-p PDB] [-n N_CLUSTERS] [-m METHOD]
                                  [-d METRIC] [--pdf-report PDF_REPORT] [-o OUTPUT_FOLDER]

   optional arguments:
   -h, --help            show this help message and exit

   Required arguments for clustering.:

   -i INPUTFILE, --inputfile INPUTFILE
                    The inputfile contains information of tiling mutagenesis screens including symbol of target
                    gene(s),targeted residue position, mutation types and phenotypic scores. Accept .txt, .cvs or
                    .xlsx fileformats. 
   -g GENE_ID, --gene_id GENE_ID
                    The symbol of targeted protein-coding gene, for example: ERCC2
   -s SAMPLES, --samples SAMPLES
                    Comma-separated sample column names.eg., "CISP,OLAP,DOX,CPT"
   -c CONTROL, --control CONTROL
                    Comma-separated control column names.eg., T0

   Optional arguments for clustering.:

   -p PDB, --pdb PDB     File path to the PDB of targeted protein structure.
   -n N_CLUSTERS, --n-clusters N_CLUSTERS
                    Number of clusters for clustering analysis.
   -m METHOD, --method METHOD
                    Clustering linkage method (default: average).
   -d METRIC, --metric METRIC
                    Clustering metric (default: euclidean).
   --pdf-report PDF_REPORT
                    Generate pdf report of clustering, visualization and annotation.
    -o OUTPUT_FOLDER, --output-folder OUTPUT_FOLDER
                    Output folder for saving the results.

2. ProTiler-Mut 3d-rra: Perform "3D-RRA" to call significant substructures in specific mutation clusters

   usage: protiler-mut.py 3d-rra [-h] -g GENE_ID -i INPUTFILE -p PDB -n N [-r NUM_PERMUTATIONS] [-t1 DISTANCE_THRESHOLD1]
                          [-t2 DISTANCE_THRESHOLD2] [-o OUTPUT_FOLDER]

   optional arguments:
   -h, --help            show this help message and exit

   Required arguments for 3D-RRA.:

   -g GENE_ID, --gene_id GENE_ID
                    The symbol of targeted protein-coding gene, for example: ERCC2
   -i INPUTFILE, --inputfile INPUTFILE
                    Path output tables file generated in cluster module which annotat the significant mutations, their
                    cluster assignment and residue position
   -p PDB, --pdb PDB     File path to the PDB of targeted protein structure
   -n N, --n N           Number of mutation samples for RRA analysis

   Optional arguments for 3D-RRA.:

   -r NUM_PERMUTATIONS, --num-permutations NUM_PERMUTATIONS
                    Number of permutations (default: 10000).
   -t1 DISTANCE_THRESHOLD1, --distance-threshold1 DISTANCE_THRESHOLD1
                    Distance threshold to identify clusters of seed mutations on 3D structure(default: 10.0 Å).
   -t2 DISTANCE_THRESHOLD2, --distance-threshold2 DISTANCE_THRESHOLD2
                    Distance threshold to identify surrounding signals near identified seed mutations(default: 5.0 Å).
   -o OUTPUT_FOLDER, --output-folder OUTPUT_FOLDER
                     Output folder for results.

3. ProTiler-Mut ppi-mapping: Perform PPI-mapping for specific mutation or substructure to identify mutaiton-associated PPIs

   usage: protiler-mut.py ppi-mapping [-h] -g GENE_ID -i INPUTFILE -f PDB_FILES -b CHAINS [-t DISTANCE_THRESHOLD]
                               [-o OUTPUT_FOLDER]

   optional arguments:
   -h, --help            show this help message and exit

   Required arguments for PPI-mapping.:

   -g GENE_ID, --gene_id GENE_ID
                    The symbol of targeted protein-coding gene, for example: ERCC2
   -i INPUTFILE, --inputfile INPUTFILE
                    Path output tables file generated in cluster module which annotat the significant mutations, their
                    cluster assignment and residue position, See example file
   -f PDB_FILES, --pdb-files PDB_FILES
                    Comma-separated list of paths of protein complex PDB files involving the target protein.
   -b CHAINS, --chains CHAINS
                    Comma-separated list of corresponding chain IDs of the target protein(e.g., A,B,A).

   Optional arguments for PPI mapping.:

   -t DISTANCE_THRESHOLD, --distance-threshold DISTANCE_THRESHOLD
                    Distance threshold to determine whether two residues interact between among different
                    chains(default: 5.0 Å).
   -o OUTPUT_FOLDER, --output-folder OUTPUT_FOLDER
                    Output folder for results.

For a detailed tutorial to run ProTiler-Mut, please refer to the video at Youtube https://www.youtube.com/@bioinforbricker