Metaclonotype discovery pipeline
Project description
Metaclonotypist
Metaclonotypist is a flexible, modular pipeline for the discovery of TCR metaclones. It is powered by the pyrepseq package for repertoire sequencing analysis.
Features
- Automated identification of T cell metaclones from repertoire sequencing data
- HLA-association analysis with statistical testing
- Modular, reproducible pipeline that combines speed with accuracy
Requirements
- Python 3.8 or later
- Install dependencies via pip (see
pyproject.toml)
Installation
pip install metaclonotypist
Note that installation might take a couple of minutes, if dependencies need to be installed.
Usage
Basic run on example data
To run the CLI with example data:
git clone https://github.com/qimmuno/metaclonotypist.git
cd metaclonotypist
pip install -e .
bash examples/run_cli_example.sh
Outputs
This will create (if successful) the following outputs in the folder examples/out:
- a volcano plot of cluster-HLA associations
- a table of significant cluster-HLA associations
- a corresponding table reporting the TCRs associated with all identified metaclones
- a table of summary statistics and parameter values
The example data is small in size so the analysis should run in <10s. The analysis is based on a dataset (in examples/data) of the 30 top-most expanded clones at the site of a tuberculin-skin test from 150 individuals with associated HLA metadata.
Run on custom data
To run on your own dataset:
metaclonotypist --tcrpath path/to/tcr.csv --hlapath path/to/hla.csv --output-dir my_results/
Refer to examples/data/ for input file format.
Citing Metaclonotypist
Please cite our preprint.
BibTex
@article{turner_tst_2025,
title = {Evolution of {T} cell responses in the tuberculin skin test reveals generalisable Mtb-reactive {T} cell metaclones},
doi = {10.1101/2025.04.12.648537},
journal = {biorXiv preprint},
author = {Turner, Carolin T and Tiffeau-Mayer, Andreas and Rosenheim, Joshua and Chandran, Aneesh and Saxena, Rishika and Zhang, Ping and Jiang, Jana and Berkeley, Michelle and Pang, Flora and Uddin, Imran and Nageswaran, Gayathri and Byrne, Suzanne and Karthikeyan, Akshay and Smidt, Werner and Ogongo, Paul and Byng-Maddick, Rachel and Capocci, Santino and Lipman, Marc and Kunst, Heike and Lozewicz, Stefan and Rasmussen, Veron and Pollara, Gabriele and Knight, Julian C and Leslie, Alasdair and Chain, Benny M and Noursadeghi, Mahdad},
year = {2025},
}
License
Metaclonotypist is released under the MIT License.
Contributing
Contributions, bug reports, and feature requests are welcome! Please open an issue or pull request on GitHub.
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