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Chaste implementation for our computational model for investigating the evolution of colonic crypts during Lynch syndrome carcinogenesis

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ComputationalColonicCrypts

ComputationalColonicCrypts is a modification and extension of the existing Chaste implementation on colonic crypt modeling for modeling Lynch syndrome carcinogenesis.

Overview

ComputationalColonicCrypts aims to be an implementation of the computational model presented in Haupt et al (2020), in preparation for the evolution of colonic crypts in Lynch syndrome carcinogenesis. The implementation is based on the Chaste software, release 2019_1. It can be included in the existing Chaste implementation by replacing some of the existing files and by adding some additional files, all available here in this repository.

Documentation

For the Chaste documentation, please read https://chaste.cs.ox.ac.uk/trac/wiki/ChasteGuides.

Preliminaries

For running the numerical simulations with Chaste, the following existing files of Chaste have to be replaced:

  • crypt/src/cell/cycle/SimpleWntCellCycleModel.cpp
  • cell_based/src/cell/cycle/AbstractPhaseBasedCellCycleModel.cpp
  • cell_based/src/population/forces/GeneralisedLinearSpringForce.cpp
  • cell_based/src/simulation/numerical_methods/ForwardEulerNumericalMethod.cpp
  • cell_based/src/population/AbstractCellPopulation.cpp
  • cell_based/src/population/AbstractCentreBasedCellPopulation.cpp

The following .cpp and .hpp files (if not stated otherwise) have to be added to the existing Chaste code:

  • all mutations except wild-type in cell_based/src/cell/properties/mutations
  • cell_based/src/population/killers/CryptFissionCellKiller
  • cell_based/src/population/killers/HomeostaticCellKiller
  • crypt/test/cell/TestColonicCryptSimulation.hpp

Execute the code

The main file is crypt/test/cell/TestColonicCryptSimulation.hpp

To compile the code, go to the build folder and

make TestColonicCryptSimulation

Run the code on one processor with

ctest -V -R TestColonicCryptSimulation

or on multiple processor to simulate multiple crypts in parallel with

mpirun -n 4 ./run

This will run the code on 4 processors.

Set parameter values

The following parameter settings can be altered in crypt/test/cell/TestColonicCryptSimulation.hpp:

  • the length of the simulation, measured in multiples of the stem cell cycle
  • the number of crypts to be simulated sequentially
  • the MLH1/MSH2 mutation status
  • initial conditions, such as number of cells and possible stem cell mutations
  • stem cell mutation rates, exchange rate, death rate
  • the number of stem cells
  • the crypt fission rate

In crypt/src/cell/cycle/SimpleWntCellCycleModel.cpp, we can change

  • the MLH1/MSH2 mutation status (this has to be in concordance with the main file)
  • effect of mutations on cell differentiation
  • mutation rate for TA cells

System Requirements

Hardware Requirements

For hardware requirements, we refer to https://chaste.cs.ox.ac.uk/trac/wiki/GettingStarted#SupportedOperatingSystems.

Software Requirements

For running the simulations, you need to install Chaste, release 2019_1 available on https://www.cs.ox.ac.uk/chaste/download.html.

OS Requirements

For OS requirements, we refer to https://chaste.cs.ox.ac.uk/chaste/tutorials/release_2019.1/.

Installation Guide

The Installation Guide for Chaste is available online https://chaste.cs.ox.ac.uk/chaste/tutorials/release_2019.1/InstallGuides/InstallGuide.html.

Further, the modified and the additional files have to be included in the Chaste folders as listed above.

License

Chaste source is released under 3-clause BSD license.

Copyright (c) 2010, The Chancellor, Masters and Scholars of the University of Oxford. All rights reserved.

Redistribution and use in source and binary forms, with or without modification, are permitted provided that the following conditions are met:

  • Redistributions of source code must retain the above copyright notice, this list of conditions and the following disclaimer.
  • Redistributions in binary form must reproduce the above copyright notice, this list of conditions and the following disclaimer in the documentation and/or other materials provided with the distribution.
  • Neither the name of the University of Oxford nor the names of its contributors may be used to endorse or promote products derived from this software without specific prior written permission.

THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.

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Chaste implementation for our computational model for investigating the evolution of colonic crypts during Lynch syndrome carcinogenesis

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