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Biology Systems Description Language (BiSDL)

This repository contains the code of the Biology Systems Description Language (BiSDL), a high-level model description language for biological processes.

Release notes

BiSDL v1.0:

  • First release of BiSDL.

BiSDL v1.1:

  • Added the conjugative plasmid transfer

BiSDL v1.2:

  • Fixed minor issues with file organization

How to cite

BiSDL Primary publications

  • L. Giannantoni, R. Bardini, A. Savino and S. D. Carlo, "Biology System Description Language (BiSDL): a modeling language for the design of multicellular synthetic biological systems", preprint available at biorXiv (https://doi.org/10.1101/2024.01.13.575499), submitted for publication in BMC Bioinformatics.

  • F. Muggianu, A. Benso, R. Bardini, E. Hu, G. Politano and S. D. Carlo, "Modeling biological complexity using Biology System Description Language (BiSDL)," 2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Madrid, Spain, 2018, pp. 713-717, doi: 10.1109/BIBM.2018.8621533.

Experimental setup

Follow these steps to setup for reproducing the experiments provided in Giannantoni et al., 2024.

  1. Install Singularity from https://docs.sylabs.io/guides/3.0/user-guide/installation.html:
  2. Clone the BiSDL repository in your home folder
git clone https://github.com/smilies-polito/bisdl.git
  1. Move to the BiSDL source subfolder, and build the singularity container with
mv bisdl/source
sudo singularity build BiSDL.sif BiSDL.def

or

mv BiSDL/source
singularity build --fakeroot BiSDL.sif BiSDL.def

Reproducing results of BiSDL case studies

BiSDL validation relies on two case studies, as described in Giannantoni et al., 2024:

The bacterial consortium

The first case study presents a proof-of-concept design in which two parts of a synthetic construct are split between two different cell types in a synthetic bacterial consortium. The overall genetic device results in lactose repressor protein (LacI)-operated gene expression regulation across cells. In particular, controller cells perform baseline production of 3-oxohexanoyl-homoserine lactone ( 3OC6HSL), an Acyl-homoserine lactones (AHL) molecular signal, hampered by a reference signal (LacI administration). On the other hand, target cells initiate the production of a reporter signal (Green Fluorescent Protein (GFP)) only when receiving the AHL molecular signal (3OC6HSL).

The RGB synthetic morphogen system

The second case study describes a synthetic morphogen system whose design involves multiple cells and their spatial interactions and organization from which a spatial pattern of red, green, and blue (RGB) fluorescent markers expression emerges.

The conjugative plasmid transfer

The third case study describes antibiotic resistance (R) conjugative plasmid transfer across bacterial cells.

Reproducing the analysis interactively within the BiSDL Singularity container

To run analyses manually launch the BiSDL Singularity container, move to /source, and launch the scripts as follows.

First of all, launch the NSS Singularity container

cd source
singularity shell --no-home --bind  /local/path/to/BiSDL:/local/path/to/home/ NSS.sif

This will run a shell within the container, and the following prompt should appear:

Singularity>

Using this prompt, follow the steps below.

The bacterial consortium

  1. Compile the provided BiSDL description:
Singularity> python3 bisdl2snakes.py examples/bacterial_consortium/bacterial_consortium.bisdl

The bisdl2snakes.py script implements the prototype BiSDL compiler generating nwn-snakes model file from BiSDL descriptions in their same folder.

  1. Run the simulation:
Singularity> python3 run_simulation.py <case_study> <experimental_condition> <simulation_steps>

The run_simulation.py script calls the prototype BiSDL simulator implemented in petrisim/ to simulate the specified case study (in this case, bacterial_consortium) and experimental condition (one among noLacI, lowLacI, and highLacI for bacterial_consortium), running for an int number of simulations steps.

To reproduce all experimental consitions for the bacterial_consortium case study, run the simulator three times:

  • noLacI
Singularity> python3 run_simulation.py bacterial_consortium noLacI 300
  • lowLacI
Singularity> python3 run_simulation.py bacterial_consortium lowLacI 300
  • highLacI
Singularity> python3 run_simulation.py bacterial_consortium highLacI 300

Each simulation run generates a results/ subfolder within the bacterial_consortium folder, where all simulation outputs are stored and organized by experimental condition.

The RGB synthetic morphogen system

  1. Compile the provided BiSDL description:
Singularity> python3 bisdl2snakes.py examples/rgb/rgb.bisdl

The bisdl2snakes.py script implements the prototype BiSDL compiler generating nwn-snakes model file from BiSDL descriptions in their same folder.

  1. Run the simulation:
Singularity> python3 run_simulation.py <case_study> <experimental_condition> <simulation_steps>

The run_simulation.py script calls the prototype BiSDL simulator implemented in petrisim/ to simulate the specified case study (in this case, rgb) and experimental condition (only rgb for rgb), running for an int number of simulations steps.

To reproduce the only experimental condition for the rgb case study, run the simulator once:

Singularity> python3 run_simulation.py rgb rgb 60

Each simulation run generates a results/ subfolder within the rgb folder, where all simulation outputs are stored and organized under the one experimental condition.

The RGB synthetic morphogen system

  1. Compile the provided BiSDL description:
Singularity> python3 bisdl2snakes.py examples/pt/pt.bisdl

The bisdl2snakes.py script implements the prototype BiSDL compiler generating nwn-snakes model file from BiSDL descriptions in their same folder.

  1. Run the simulation:
Singularity> python3 run_simulation.py <case_study> <experimental_condition> <simulation_steps>

The run_simulation.py script calls the prototype BiSDL simulator implemented in petrisim/ to simulate the specified case study (in this case, pt) and experimental condition (only pt for pt), running for an int number of simulations steps.

To reproduce the only experimental condition for the pt case study, run the simulator once:

Singularity> python3 run_simulation.py pt pt 60

Each simulation run generates a results/ subfolder within the pt folder, where all simulation outputs are stored and organized under the one experimental condition.

Reproducing the analysis running the BiSDL Singularity container

To reproduce the analyses from Giannantoni et al., 2024, run the BiSDL.sif container with the required commandline arguments: a keyword to indicate the case study (bacterial_consortium or rgb).

The bacterial consortium

singularity run --no-home --bind  /local/path/to/BiSDL:/local/path/to/home/ BiSDL.sif bacterial_consortium

The RGB synthetic morphogen system

singularity run --no-home --bind  /local/path/to/BiSDL:/local/path/to/home/ BiSDL.sif rgb

The plasmid transfer

singularity run --no-home --bind  /local/path/to/BiSDL:/local/path/to/home/ BiSDL.sif pt

Repository structure

|
├── bisdl_language                    // The implementation of the BiSDL language
|    ├── gen                          // Code implementing the parser and lexer of the BiSDL language 
|    |    └── ...
|    ├── impl                         // Code supporting the compilation of the BiSDL language into nwn-snakes models
|    |    └── ...
|    └── Module.g4                    // BiSDL grammar Module
|   
├── examples                                    // The two case studies provided in Giannantoni et al., 2024
|    |
|    ├── bacterial_consortium                   // The bacterial_consortium case study provided in Giannantoni et al., 2024
|    |     ├── bacterial_consortium.bisdl       // BiSDL description of the bacterial_consortium case study
|    |     ├── bacterial_consortium.py          // Python nwn-snakes model file compiled from BiSDL description of the bacterial_consortium case study
|    |     └── results                          // Simulation results for different experimental conditions in the bacterial_consortium case study
|    |          ├── highLacI                    // Simulation results for the highLacI experimental condition in the bacterial_consortium case study
|    |          |    └── ...                    // .csv marking files and .png simulation evolution plots
|    |          ├── lowLacI                     // Simulation results for the lowLacI experimental condition in the bacterial_consortium case study
|    |          |    └── ...                    // .csv marking files and .png simulation evolution plots
|    |          ├── noLacI                      // Simulation results for the noLacI experimental condition in the bacterial_consortium case study
|    |          |    └── ...                    // .csv marking files and .png simulation evolution plots
|    |          └── topology                    // Visualized network architectures for the bacterial_consortium case study
|    | 
|    | 
|    ├── rgb                     // The RGB synthetic morphogen system case study provided in Giannantoni et al., 2024
|    |    ├── rgb.bisdl          // BiSDL description of the rgb case study
|    |    ├── rgb.py             // Python nwn-snakes model file compiled from BiSDL description of the rgb case study
|    |    └── results           // Simulation results for the only experimental condition in the rgb case study
|    |          ├── rgb          // Simulation results for the only experimental condition in the rgb case study
|    |          |    └── ...     // .csv marking files and .png simulation evolution plots
|    |          └── topology     // Visualized network architectures for the rgb case study
|    | 
|    | 
|    └── pt                     // The plasmid transfer (pt) case study provided in Giannantoni et al., 2024
|         ├── pt.bisdl          // BiSDL description of the pt case study
|         ├── pt.py             // Python nwn-snakes model file compiled from BiSDL description of the pt case study
|         └── results          // Simulation results for the only experimental condition in the pt case study
|               ├── pt          // Simulation results for the only experimental condition in the pt case study
|               |    └── ...    // .csv marking files and .png simulation evolution plots
|               └── topology    // Visualized network architectures for the pt case study
|   
├── petrisim                                    // Python code implementing the petrisim prototype simulator for nwn-snakes models
|    ├── simulator.py
|    └── utils.py
|  
├── .gitignore                                  // .gitignore file for the BiSDL repository
|  
├── BiSDL.def                                   // The BiSDL Singularity recipe file
|  
├── bisdl2snakes.py                             // Python code implementing the prototype BiSDL compiler generating nwn-snakes models 
|  
├── run_simulation.py                           // Python code running simulations for the case studies provided in Giannantoni et al., 2024
|    
└── README.md                                   // This README file