AbstractTissue.cpp

/*

Copyright (C) University of Oxford, 2005-2010

University of Oxford means the Chancellor, Masters and Scholars of the
University of Oxford, having an administrative office at Wellington
Square, Oxford OX1 2JD, UK.

This file is part of Chaste.

Chaste is free software: you can redistribute it and/or modify it
under the terms of the GNU Lesser General Public License as published
by the Free Software Foundation, either version 2.1 of the License, or
(at your option) any later version.

Chaste is distributed in the hope that it will be useful, but WITHOUT
ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or
FITNESS FOR A PARTICULAR PURPOSE.  See the GNU Lesser General Public
License for more details. The offer of Chaste under the terms of the
License is subject to the License being interpreted in accordance with
English Law and subject to any action against the University of Oxford
being under the jurisdiction of the English Courts.

You should have received a copy of the GNU Lesser General Public License
along with Chaste. If not, see <http://www.gnu.org/licenses/>.

*/

#include "AbstractTissue.hpp"
#include "AbstractOdeBasedCellCycleModel.hpp"

template<unsigned DIM>
AbstractTissue<DIM>::AbstractTissue(std::vector<TissueCell>& rCells,
                                    const std::vector<unsigned> locationIndices)
    : mCells(rCells.begin(), rCells.end()),
      mTissueContainsMesh(false),
      mpMutationStateRegistry(CellMutationStateRegistry::Instance()->TakeOwnership())
{
    // There must be at least one cell
    assert(mCells.size() > 0);

    // To avoid double-counting problems, clear the passed-in cells vector
    rCells.clear();

    if (!locationIndices.empty())
    {
        // There must be a one-one correspondence between cells and location indices
        if (mCells.size() != locationIndices.size())
        {
            EXCEPTION("There is not a one-one correspondence between cells and location indices");
        }
    }

    // Set up the map between location indices and cells
    std::list<TissueCell>::iterator it = mCells.begin();
    for (unsigned i=0; it != mCells.end(); ++it, ++i)
    {
        unsigned index = locationIndices.empty() ? i : locationIndices[i]; // assume that the ordering matches
        mLocationCellMap[index] = &(*it);
        mCellLocationMap[&(*it)] = index;
    }

    // Initialise cell counts to zero
    mCellProliferativeTypeCount = std::vector<unsigned>(NUM_CELL_PROLIFERATIVE_TYPES);
    for (unsigned i=0; i<mCellProliferativeTypeCount.size(); i++)
    {
        mCellProliferativeTypeCount[i] = 0;
    }

    mCellCyclePhaseCount = std::vector<unsigned>(NUM_CELL_CYCLE_PHASES);
    for (unsigned i=0; i<mCellCyclePhaseCount.size(); i++)
    {
        mCellCyclePhaseCount[i] = 0;
    }
}

template<unsigned DIM>
void AbstractTissue<DIM>::InitialiseCells()
{
    for (std::list<TissueCell>::iterator iter=mCells.begin(); iter!=mCells.end(); ++iter)
    {
        iter->InitialiseCellCycleModel();
    }
}

template<unsigned DIM>
std::list<TissueCell>& AbstractTissue<DIM>::rGetCells()
{
    return mCells;
}

template<unsigned DIM>
bool AbstractTissue<DIM>::HasMesh()
{
    return mTissueContainsMesh;
}

template<unsigned DIM>
unsigned AbstractTissue<DIM>::GetNumRealCells()
{
    unsigned counter = 0;
    for (typename AbstractTissue<DIM>::Iterator cell_iter=this->Begin(); cell_iter!=this->End(); ++cell_iter)
    {
        counter++;
    }
    return counter;
}

template<unsigned DIM>
void AbstractTissue<DIM>::SetCellAncestorsToLocationIndices()
{
    for (typename AbstractTissue<DIM>::Iterator cell_iter=this->Begin(); cell_iter!=this->End(); ++cell_iter)
    {
        cell_iter->SetAncestor(mCellLocationMap[&(*cell_iter)]);
    }
}

template<unsigned DIM>
std::set<unsigned> AbstractTissue<DIM>::GetCellAncestors()
{
    std::set<unsigned> remaining_ancestors;
    for (typename AbstractTissue<DIM>::Iterator cell_iter=this->Begin(); cell_iter!=this->End(); ++cell_iter)
    {
        remaining_ancestors.insert(cell_iter->GetAncestor());
    }
    return remaining_ancestors;
}

template<unsigned DIM>
std::vector<unsigned> AbstractTissue<DIM>::GetCellMutationStateCount()
{
    if (TissueConfig::Instance()->GetOutputCellMutationStates()==false)
    {
        EXCEPTION("Call TissueConfig::Instance()->SetOutputCellMutationStates(true) before using this function");
    }

    // An ordering must have been specified for cell mutation states
    SetDefaultMutationStateOrdering();

    const std::vector<boost::shared_ptr<AbstractCellMutationState> >& r_mutation_states
        = GetMutationRegistry()->rGetAllMutationStates();

    std::vector<unsigned> cell_mutation_state_count(r_mutation_states.size());
    for (unsigned i=0; i<r_mutation_states.size(); i++)
    {
        cell_mutation_state_count[i] = r_mutation_states[i]->GetCellCount();
    }
    return cell_mutation_state_count;
}

template<unsigned DIM>
const std::vector<unsigned>& AbstractTissue<DIM>::rGetCellProliferativeTypeCount() const
{
    if (TissueConfig::Instance()->GetOutputCellProliferativeTypes()==false)
    {
        EXCEPTION("Call TissueConfig::Instance()->SetOutputCellProliferativeTypes(true) before using this function");
    }
    return mCellProliferativeTypeCount;
}

template<unsigned DIM>
const std::vector<unsigned>& AbstractTissue<DIM>::rGetCellCyclePhaseCount() const
{
    if (TissueConfig::Instance()->GetOutputCellCyclePhases()==false)
    {
        EXCEPTION("Call TissueConfig::Instance()->SetOutputCellCyclePhases(true) before using this function");
    }
    return mCellCyclePhaseCount;
}

template<unsigned DIM>
TissueCell& AbstractTissue<DIM>::rGetCellUsingLocationIndex(unsigned index)
{
    // Get a pointer to the cell corresponding to this location index
    TissueCell* p_cell = mLocationCellMap[index];

    // Unless this pointer is null, return a reference to the cell
    if (p_cell)
    {
        return *p_cell;
    }
    else
    {
        EXCEPTION("Location index input argument does not correspond to a TissueCell");
    }
}

template<unsigned DIM>
unsigned AbstractTissue<DIM>::GetLocationIndexUsingCell(TissueCell& rCell)
{
    return mCellLocationMap[&rCell];
}

template<unsigned DIM>
boost::shared_ptr<CellMutationStateRegistry> AbstractTissue<DIM>::GetMutationRegistry()
{
    return mpMutationStateRegistry;
}

template<unsigned DIM>
void AbstractTissue<DIM>::SetDefaultMutationStateOrdering()
{
    boost::shared_ptr<CellMutationStateRegistry> p_registry = GetMutationRegistry();
    if (!p_registry->HasOrderingBeenSpecified())
    {
        std::vector<boost::shared_ptr<AbstractCellMutationState> > mutations;
        mutations.push_back(p_registry->Get<WildTypeCellMutationState>());
        mutations.push_back(p_registry->Get<LabelledCellMutationState>());
        mutations.push_back(p_registry->Get<ApcOneHitCellMutationState>());
        mutations.push_back(p_registry->Get<ApcTwoHitCellMutationState>());
        mutations.push_back(p_registry->Get<BetaCateninOneHitCellMutationState>());
        p_registry->SpecifyOrdering(mutations);
    }
}

//                             Output methods                               //


template<unsigned DIM>
void AbstractTissue<DIM>::CreateOutputFiles(const std::string& rDirectory, bool cleanOutputDirectory)
{
    // Helper pointer
    TissueConfig* p_config = TissueConfig::Instance();

    OutputFileHandler output_file_handler(rDirectory, cleanOutputDirectory);
    mpVizNodesFile = output_file_handler.OpenOutputFile("results.viznodes");
    mpBoundaryNodesFile = output_file_handler.OpenOutputFile("results.vizboundarynodes");
    mpVizCellProliferativeTypesFile = output_file_handler.OpenOutputFile("results.vizcelltypes");

    if (p_config->GetOutputCellAncestors())
    {
        mpCellAncestorsFile = output_file_handler.OpenOutputFile("results.vizancestors");
    }
    if (p_config->GetOutputCellMutationStates())
    {
        mpCellMutationStatesFile = output_file_handler.OpenOutputFile("cellmutationstates.dat");
        *mpCellMutationStatesFile << "Time\t Healthy\t Labelled\t APC_1\t APC_2\t BETA_CAT \n";
    }
    if (p_config->GetOutputCellProliferativeTypes())
    {
        mpCellProliferativeTypesFile = output_file_handler.OpenOutputFile("celltypes.dat");
    }
    if (p_config->GetOutputCellVariables())
    {
        mpCellVariablesFile = output_file_handler.OpenOutputFile("cellvariables.dat");
    }
    if (p_config->GetOutputCellCyclePhases())
    {
        mpCellCyclePhasesFile = output_file_handler.OpenOutputFile("cellcyclephases.dat");
    }
    if (p_config->GetOutputCellAges())
    {
        mpCellAgesFile = output_file_handler.OpenOutputFile("cellages.dat");
    }
    if (p_config->GetOutputCellIdData())
    {
        mpCellIdFile = output_file_handler.OpenOutputFile("loggedcell.dat");
    }
}

template<unsigned DIM>
void AbstractTissue<DIM>::CloseOutputFiles()
{
    // Helper pointer
    TissueConfig* p_config = TissueConfig::Instance();

    mpVizNodesFile->close();
    mpBoundaryNodesFile->close();
    mpVizCellProliferativeTypesFile->close();

    if (p_config->GetOutputCellMutationStates())
    {
        mpCellMutationStatesFile->close();
    }
    if (p_config->GetOutputCellProliferativeTypes())
    {
        mpCellProliferativeTypesFile->close();
    }
    if (p_config->GetOutputCellVariables())
    {
        mpCellVariablesFile->close();
    }
    if (p_config->GetOutputCellCyclePhases())
    {
        mpCellCyclePhasesFile->close();
    }
    if (p_config->GetOutputCellAncestors())
    {
        mpCellAncestorsFile->close();
    }
    if (p_config->GetOutputCellAges())
    {
        mpCellAgesFile->close();
    }
    if (p_config->GetOutputCellIdData())
    {
        mpCellIdFile->close();
    }
}

template<unsigned DIM>
void AbstractTissue<DIM>::GenerateCellResults(unsigned locationIndex,
                                              std::vector<unsigned>& rCellProliferativeTypeCounter,
                                              std::vector<unsigned>& rCellCyclePhaseCounter)
{
    // Helper pointer
    TissueConfig* p_config = TissueConfig::Instance();

    unsigned colour = STEM_COLOUR;

    TissueCell* p_cell = mLocationCellMap[locationIndex];

    if (p_config->GetOutputCellCyclePhases())
    {
        // Update rCellCyclePhaseCounter
        switch (p_cell->GetCellCycleModel()->GetCurrentCellCyclePhase())
        {
            case G_ZERO_PHASE:
                rCellCyclePhaseCounter[0]++;
                break;
            case G_ONE_PHASE:
                rCellCyclePhaseCounter[1]++;
                break;
            case S_PHASE:
                rCellCyclePhaseCounter[2]++;
                break;
            case G_TWO_PHASE:
                rCellCyclePhaseCounter[3]++;
                break;
             case M_PHASE:
                rCellCyclePhaseCounter[4]++;
                break;
            default:
                NEVER_REACHED;
        }
    }

    if (p_config->GetOutputCellAncestors())
    {
        // Set colour dependent on cell ancestor and write to file
        colour = p_cell->GetAncestor();
        if (colour == UNSIGNED_UNSET)
        {
            // Set the file to -1 to mark this case.
            colour = 1;
            *mpCellAncestorsFile << "-";
        }
        *mpCellAncestorsFile << colour << " ";
    }

    // Set colour dependent on cell type
    switch (p_cell->GetCellProliferativeType())
    {
        case STEM:
            colour = STEM_COLOUR;
            if (p_config->GetOutputCellProliferativeTypes())
            {
                rCellProliferativeTypeCounter[0]++;
            }
            break;
        case TRANSIT:
            colour = TRANSIT_COLOUR;
            if (p_config->GetOutputCellProliferativeTypes())
            {
                rCellProliferativeTypeCounter[1]++;
            }
            break;
        case DIFFERENTIATED:
            colour = DIFFERENTIATED_COLOUR;
            if (p_config->GetOutputCellProliferativeTypes())
            {
                rCellProliferativeTypeCounter[2]++;
            }
            break;
        case APOPTOTIC:
            colour = APOPTOSIS_COLOUR;
            if (p_config->GetOutputCellProliferativeTypes())
            {
                rCellProliferativeTypeCounter[3]++;
            }
            break;
        default:
            NEVER_REACHED;
    }

    if (p_config->GetOutputCellMutationStates())
    {
        // Set colour dependent on cell mutation state
        if (!p_cell->GetMutationState()->IsType<WildTypeCellMutationState>())
        {
            colour = p_cell->GetMutationState()->GetColour();
        }
    }

    if (p_cell->HasApoptosisBegun())
    {
        // For any type of cell set the colour to this if it is undergoing apoptosis.
        colour = APOPTOSIS_COLOUR;
    }

    // Write cell variable data to file if required
    if ( p_config->GetOutputCellVariables() && dynamic_cast<AbstractOdeBasedCellCycleModel*>(p_cell->GetCellCycleModel()) )
    {
        // Write location index corresponding to cell
        *mpCellVariablesFile << locationIndex << " ";

        // Write cell variables
        std::vector<double> proteins = (static_cast<AbstractOdeBasedCellCycleModel*>(p_cell->GetCellCycleModel()))->GetProteinConcentrations();
        for (unsigned i=0; i<proteins.size(); i++)
        {
            *mpCellVariablesFile << proteins[i] << " ";
        }
    }

    // Write cell age data to file if required
    if (p_config->GetOutputCellAges())
    {
        // Write location index corresponding to cell
        *mpCellAgesFile << locationIndex << " ";

        // Write cell location
        c_vector<double, DIM> cell_location = GetLocationOfCellCentre(*p_cell);

        for (unsigned i=0; i<DIM; i++)
        {
            *mpCellAgesFile << cell_location[i] << " ";
        }

        // Write cell age
        *mpCellAgesFile << p_cell->GetAge() << " ";
    }

    *mpVizCellProliferativeTypesFile << colour << " ";
}

template<unsigned DIM>
void AbstractTissue<DIM>::WriteCellResultsToFiles(std::vector<unsigned>& rCellProliferativeTypeCounter,
                                                  std::vector<unsigned>& rCellCyclePhaseCounter)
{
    // Helper pointer
    TissueConfig* p_config = TissueConfig::Instance();

    *mpVizCellProliferativeTypesFile << "\n";

    if (p_config->GetOutputCellAncestors())
    {
        *mpCellAncestorsFile << "\n";
    }

    // Write cell mutation state data to file if required
    if (p_config->GetOutputCellMutationStates())
    {
        // An ordering must be specified for cell mutation states
        SetDefaultMutationStateOrdering();

        const std::vector<boost::shared_ptr<AbstractCellMutationState> >& r_mutation_states
            = GetMutationRegistry()->rGetAllMutationStates();

        for (unsigned i=0; i<r_mutation_states.size(); i++)
        {
            *mpCellMutationStatesFile << r_mutation_states[i]->GetCellCount() << "\t";
        }
        *mpCellMutationStatesFile << "\n";
    }

    // Write cell type data to file if required
    if (p_config->GetOutputCellProliferativeTypes())
    {
        for (unsigned i=0; i<mCellProliferativeTypeCount.size(); i++)
        {
            mCellProliferativeTypeCount[i] = rCellProliferativeTypeCounter[i];
            *mpCellProliferativeTypesFile << rCellProliferativeTypeCounter[i] << "\t";
        }
        *mpCellProliferativeTypesFile << "\n";
    }

    if (p_config->GetOutputCellVariables())
    {
        *mpCellVariablesFile << "\n";
    }

    // Write cell cycle phase data to file if required
    if (p_config->GetOutputCellCyclePhases())
    {
        for (unsigned i=0; i<mCellCyclePhaseCount.size(); i++)
        {
            mCellCyclePhaseCount[i] = rCellCyclePhaseCounter[i];
            *mpCellCyclePhasesFile << rCellCyclePhaseCounter[i] << "\t";
        }
        *mpCellCyclePhasesFile << "\n";
    }

    // Write cell age data to file if required
    if (p_config->GetOutputCellAges())
    {
        *mpCellAgesFile << "\n";
    }
}

template<unsigned DIM>
void AbstractTissue<DIM>::WriteTimeAndNodeResultsToFiles()
{
    double time = SimulationTime::Instance()->GetTime();

    *mpVizNodesFile << time << "\t";
    *mpBoundaryNodesFile << time << "\t";

    // Write node data to file
    for (unsigned node_index=0; node_index<GetNumNodes(); node_index++)
    {
        // Hack that covers the case where the node is associated with a cell that has just been killed (#1129)
        bool node_corresponds_to_dead_cell = false;
        if (mLocationCellMap[node_index])
        {
            node_corresponds_to_dead_cell = mLocationCellMap[node_index]->IsDead();
        }

        // Write node data to file
        if ( !(GetNode(node_index)->IsDeleted()) && !node_corresponds_to_dead_cell)
        {
            const c_vector<double,DIM>& position = GetNode(node_index)->rGetLocation();

            for (unsigned i=0; i<DIM; i++)
            {
                *mpVizNodesFile << position[i] << " ";
            }
            *mpBoundaryNodesFile << GetNode(node_index)->IsBoundaryNode() << " ";
        }
    }
    *mpVizNodesFile << "\n";
    *mpBoundaryNodesFile << "\n";
}

template<unsigned DIM>
void AbstractTissue<DIM>::WriteResultsToFiles()
{
    // Helper pointer
    TissueConfig* p_config = TissueConfig::Instance();

    WriteTimeAndNodeResultsToFiles();

    double time = SimulationTime::Instance()->GetTime();

    *mpVizCellProliferativeTypesFile << time << "\t";

    if (p_config->GetOutputCellAncestors())
    {
        *mpCellAncestorsFile << time << "\t";
    }
    if (p_config->GetOutputCellMutationStates())
    {
        *mpCellMutationStatesFile << time << "\t";
    }
    if (p_config->GetOutputCellProliferativeTypes())
    {
        *mpCellProliferativeTypesFile << time << "\t";
    }
    if (p_config->GetOutputCellVariables())
    {
        *mpCellVariablesFile << time << "\t";
    }
    if (p_config->GetOutputCellCyclePhases())
    {
        *mpCellCyclePhasesFile << time << "\t";
    }
    if (p_config->GetOutputCellAges())
    {
        *mpCellAgesFile << time << "\t";
    }

    GenerateCellResultsAndWriteToFiles();

    // Write logged cell data if required
    if (p_config->GetOutputCellIdData())
    {
        WriteCellIdDataToFile();
    }
}

template<unsigned DIM>
void AbstractTissue<DIM>::WriteCellIdDataToFile()
{
    // Write time to file
    *mpCellIdFile << SimulationTime::Instance()->GetTime();

    for (typename AbstractTissue<DIM>::Iterator cell_iter = Begin();
         cell_iter != End();
         ++cell_iter)
    {
        unsigned cell_id = cell_iter->GetCellId();
        unsigned location_index = mCellLocationMap[&(*cell_iter)];
        *mpCellIdFile << " " << cell_id << " " << location_index;

        c_vector<double, DIM> coords = GetLocationOfCellCentre(*cell_iter);
        for (unsigned i=0; i<DIM; i++)
        {
            *mpCellIdFile << " " << coords[i];
        }
    }
    *mpCellIdFile << "\n";
}


// Explicit instantiation

template class AbstractTissue<1>;
template class AbstractTissue<2>;
template class AbstractTissue<3>;