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Modeling host-parasite interactions

Zenodo DOI (concept — all versions)

Generation of models for human hepatocyte and plasmodium falciparum contextualized to the nutrient environment on the host hepatocyte. Analysis of nutritional interactions between host and parasite and host gene essentiality for parasite survival. Companion code for: Maurizio M, Masid M, et al. "Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites." Nature Communications 15, 6145 (2024). doi:10.1038/s41467-024-50405-x

Requirements

You will need to have Git LFS in order to properly download the binary files:

git clone https://github.com/EPFL-LCSB/host_parasite_interactions.git /path/to/host_parasite_interactions
cd /path/to/host_parasite_interactions
git lfs install
git lfs pull

The scripts have been developed with Matlab 2021b, and CPLEX 12.10 (freely downloadable with the IBM Academic initiative), and successfully ran on several other versions of both softwares. However, it is important to respect the IBM compatibility specs sheets between Matlab, CPLEX, and the computer OS - available on IBM's website.

This module requires matTFA, redGEM

Generating host, parasite and host-parasite metabolic models and performing gene essentiality analysis

Run the script run_host_parasite_interactions.m from the main folder. There are four steps: 1. Generation of a hepatocyte model from the human Recon 3D model 2. Generation of parasitosomes for Plasmodium falciparum 3. Reconstruction of an integrated host-parasite model 4. Performing gene essentiality analysis

Associated data

The CRISPR screen and RNA-seq data underlying the paper are deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under BioProject PRJEB73635 (RNA-seq samples: ERS16273013, ERS16273014, ERS16273015, ERS18408949, ERS18408950, ERS18408951).

Citation

If you use this software, please cite both the archived software and the paper.

  • Software archive (Zenodo): concept DOI 10.5281/zenodo.20543332 (all versions; resolves to the latest). This release v1.0.0: 10.5281/zenodo.20543333.
  • Paper: Maurizio M, Masid M, Woods K, et al. Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites. Nature Communications 15, 6145 (2024). doi:10.1038/s41467-024-50405-x

A machine-readable CITATION.cff is provided at the repository root.

License

The source code in this repository (the code/ directory and run_host_parasite_interactions.m) is released under the Apache-2.0 license — see the LICENSE file.

The data and models under data/ and models/ are not covered by Apache-2.0. Several are third-party datasets (Recon3D, BiGG, the Human Protein Atlas, …) redistributed under their own — in some cases non-commercial — licenses. See DATA_LICENSES.md for per-file provenance, license and citation.

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Generating host-parasite metabolic models to investigate the dependence of the parasite on the host's metabolic genes

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