Use cases#

We provide users with three different use cases to show the main features of our package. These files are available in the examples folder on GitHub and can be used as templates to design more complex studies and extended to fit the users’ needs.

We specifically implemented (i) an idealized scenario where cells were placed in a radial arrangment and neurite outgrowth was promoted towards their common core, (ii) a numerical study based on this idealized case and (iii) a tissue-scale simulation.

Idealized rosette formation#

"""Script to simulate the formation of Homer-Wright rosettes."""

import numpy as np

from neurorosettes.simulation import Simulation, Container


def create_tissue(container: Container) -> None:
    """Creates and registers new neurons in the simulation world."""
    radius = 24.0
    number_of_cells = 9
    t = np.linspace(0, 2*np.pi, number_of_cells, endpoint=False)

    x = radius * np.cos(t)
    y = radius * np.sin(t)

    for x_coord, y_coord in zip(x, y):
        neuron = container.create_new_neuron(coordinates=[x_coord, y_coord, 0])
        neuron.set_outgrowth_axis(np.subtract(np.zeros(3), neuron.cell.position))

def main():
    # Initialize simulation objects
    sim_world = Simulation.from_file("config/config.yml")
    # Create initial configuration
    create_tissue(sim_world.container)
    # Plot the current state of the simulation
    sim_world.container.animator.set_camera(height=400.0)
    sim_world.container.animator.show()
    # Run the simulation to check if springs work
    sim_world.run()
    # Plot the results (mark interactive as False to automatically  close the window)
    sim_world.container.animator.show(interactive=True)


if __name__ == "__main__":
    main()

Numerical study#

"""Script to perform a parameter study on the cell mechanics parameters that regulate the tissue architecture."""
from typing import Dict
from pathlib import Path
import json
from itertools import count

from neurorosettes.simulation import Simulation, Container
from neurorosettes.utilities import HexagonalTissue
from neurorosettes.grid import OneLevelDensityCheck

# Cell-cell interactions
cell_cell_adhesion = 5.0
cell_cell_repulsion = [15.0, 25.0, 50.0]
# Cell-neurite interactions
cell_neurite_adhesion = 5.0
cell_neurite_repulsion = [15.0, 25.0, 50.0]
# Neurite-neurite interactions
neurite_neurite_adhesion = 5.0
neurite_neurite_repulsion = [15.0, 25.0, 50.0]

# Replicates for each condition
NUMBER_OF_REPLICATES = 3

# Contact inhibition function
DENSITY_CHECK = OneLevelDensityCheck(max_neighbors=19)


def set_density_check(container: Container) -> None:
    """Adds the contact inhibition function to the simulation."""
    container.set_density_check(DENSITY_CHECK)


def create_tissue(container: Container) -> None:
    """Creates and registers new neurons in the simulation world."""
    # Initial cell positions
    tissue = HexagonalTissue(size=160, spacing=20).get_coordinates()
    # Create a neuron with two neurites
    for cell in tissue:
        container.create_new_neuron(coordinates=cell)


def simulation(sim_world: Simulation) -> None:
    """Adds any additional functions to the container and runs the simulation."""
    # Add additional functions to the simulation (i.g., contact inhibition)
    set_density_check(sim_world.container)
    # Create initial configuration
    create_tissue(sim_world.container)
    # Plot the current state of the simulation
    sim_world.container.animator.set_camera(height=600.0)
    sim_world.container.animator.show()
    # Run the simulation to check if springs work
    sim_world.run()


def create_params_dict(
    cca: float, ccr: float, cna: float, cnr: float, nna: float, nnr: float
) -> Dict[str, float]:
    """Returns a dictionary with the name of the varied parameters and corresponding values."""
    return {
        "cell-cell adhesion": cca,
        "cell-cell repulsion": ccr,
        "cell-neurite adhesion": cna,
        "cell_neurite repulsion": cnr,
        "neurite-neurite adhesion": nna,
        "neurite-neurite repulsion": nnr,
    }


def main():
    # Simple counter to make sure that output files are stored in unique folders
    sim_counter = count(start=0)

    # Loop through the interaction combinations
    for nnr in neurite_neurite_repulsion:
        for cnr in cell_neurite_repulsion:
            for ccr in cell_cell_repulsion:
                # Store the current iteration's parameters in a JSON file
                # First create a dict with this information
                parameters = create_params_dict(
                    cell_cell_adhesion,
                    ccr,
                    cell_neurite_adhesion,
                    cnr,
                    neurite_neurite_adhesion,
                    nnr,
                )

                # Then store the data in a JSON file
                folder_name = next(sim_counter)
                filepath = Path(f"output/{folder_name}/params.json")
                filepath.parent.mkdir(parents=True, exist_ok=True)

                with open(filepath, "w") as outfile:
                    json.dump(parameters, outfile)

                for i in range(NUMBER_OF_REPLICATES):
                    # Load the data from the configuration file to create a simulation instance
                    sim_world = Simulation.from_file("config/config.yml")

                    # Update the interaction coefficients based on the current iteration
                    sim_world.container.sphere_int.adhesion_coefficient = cell_cell_adhesion
                    sim_world.container.sphere_int.repulsion_coefficient = ccr
                    sim_world.container.sphere_cylinder_int.adhesion_coefficient = cell_neurite_adhesion
                    sim_world.container.sphere_cylinder_int.repulsion_coefficient = cnr
                    sim_world.container.cylinder_int.adhesion_coefficient = neurite_neurite_adhesion
                    sim_world.container.cylinder_int.repulsion_coefficient = nnr

                    # Run the simulation
                    simulation(sim_world)

                    # Plot and save the results (mark interactive as False to automatically  close the window)
                    sim_world.container.animator.show(interactive=False)
                    sim_world.container.animator.save_screenshot(f"output/{folder_name}/replicate{i}.png")
                    sim_world.container.animator.plotter.close()


if __name__ == "__main__":
    main()

Tissue-scale#

"""Script to perform a parameter study on the cell mechanics parameters that regulate the tissue architecture."""

from neurorosettes.simulation import Simulation, Container
from neurorosettes.utilities import HexagonalTissue
from neurorosettes.grid import OneLevelDensityCheck


# Contact inhibition function
DENSITY_CHECK = OneLevelDensityCheck(max_neighbors=19)


def set_density_check(container: Container) -> None:
    """Adds the contact inhibition function to the simulation."""
    container.set_density_check(DENSITY_CHECK)


def create_tissue(container: Container) -> None:
    """Creates and registers new neurons in the simulation world."""
    # Initial cell positions
    tissue = HexagonalTissue(size=190, spacing=20).get_coordinates()
    # Create a neuron with two neurites
    for cell in tissue:
        container.create_new_neuron(coordinates=cell)


def simulation(sim_world: Simulation) -> None:
    """Adds any additional functions to the container and runs the simulation."""
    # Add additional functions to the simulation (i.g., contact inhibition)
    set_density_check(sim_world.container)
    # Create initial configuration
    create_tissue(sim_world.container)
    # Plot the current state of the simulation
    sim_world.container.animator.set_camera(height=400.0)
    sim_world.container.animator.show()
    #sim_world.container.animator.save_screenshot(f"output/start")
    #sim_world.save_meshes("output/start")
    # Run the simulation to check if springs work
    sim_world.run()

def main():
    # Load the data from the configuration file to create a simulation instance
    sim_world = Simulation.from_file("config/config.yml")

    # Run the simulation
    simulation(sim_world)

    # Plot and save the results (mark interactive as False to automatically close the window)
    #sim_world.container.animator.show(interactive=True)
    sim_world.container.animator.save_screenshot(f"output/no_diff")
    sim_world.save_meshes("output/no_diff")
    #sim_world.container.animator.plotter.close()


if __name__ == "__main__":
    main()