// *******initialize******* domain with cells
void resetCells() {
// int radius=50; dont think this is used
Cells = new int[size][size];
carriedmutation = new int[size][size];
// Fill the domain with healthy cells 0's first.
for (int i = 0; i < size; i++)
for (int j = 0; j < size; j++) {
Cells[i][j] = 0;
carriedmutation[i][j] = 0;
}
Cells[centre][centre] = 1; // initialize with a stem cell if you like
carriedmutation[centre][centre] = 1; // the first cancer cell carries the tag '1' to start
genomeToMod = new StringBuilder(carriedGenome[centre][centre]);
genomeToMod.setCharAt(mutationNum - 1, '1'); // daughter carries new carriedGenome
carriedGenome[centre][centre] = genomeToMod;
// genomeToMod = carriedGenome[centre][centre];
}
// main CELL CA loop************
public boolean iterateCells() {
/*
// modify consumption matrix
for (int i=0;i<size;i++)
for (int j=0;j<size;j++) consumption[i][j] = consumptionBasal[Cells[i][j]];
*/
//
if (cellList == null) cellList = new Bag(size * size);
for (int i = 0; i < size; i++)
for (int j = 0; j < size; j++) {
if (Cells[i][j]
< 4) { // All tumour cell types have Cell > 0, now 0 corresponds to 'healthy cells' that
// consume at basal rate only
int[] p = new int[2];
p[0] = i;
p[1] = j;
cellList.add(p);
if (Cells[i][j] == 1) {
stem_cells_this_TS++;
} else if (Cells[i][j] == 2 || Cells[i][j] == 3) {
non_stem_cells_this_TS++;
}
}
}
while (cellList.size() != 0) {
// Select the next lattice element at random
int randomElemIndex = 0;
if (cellList.size() > 1) randomElemIndex = random.nextInt(cellList.size() - 1);
int[] point = (int[]) cellList.get(randomElemIndex);
int rI = point[0];
int rJ = point[1];
cellList.remove(randomElemIndex); // Remove it from the cell list
int cell = Cells[rI][rJ];
// Cell death
// if ((Oxygen[rI][rJ]<hypoxia)) {
if ((random.nextFloat() < deathprob) && Cells[rI][rJ] > 0) { // x% chances of dying
Age[rI][rJ] = 0;
if (Cells[rI][rJ] == 1) stemDeathCounter[rI][rJ]++;
if (Cells[rI][rJ] < 4) {
// TACDeathCounter[rI][rJ]++;
Cells[rI][rJ] = 4; // was 0, now making necrotic area (truly empty)
deaths++;
stemBirthCounter[rI][rJ] = 0;
carriedmutation[rI][rJ] = 0; // empty space now has no mutations
carriedGenome[rI][rJ] = initGenome; // empty space now has no mutations
}
} else if ((cell == 3)
&& (Age[rI][rJ]
> 100 * maxMatureCellAge)) { // added * to allow for an update each celltimestep/x
// **************************
Age[rI][rJ] = 0;
Cells[rI][rJ] = 4; // was 0, now making necrotic area (truly empty)
// TACDeathCounter[rI][rJ]++;
deaths++;
} else if ((radiotherapy) && (cell == 2) && (random.nextFloat() > Oxygen[rI][rJ])) {
// Radiotherapy
Age[rI][rJ] = 0;
if (Cells[rI][rJ] == 1) stemDeathCounter[rI][rJ]++;
if ((Cells[rI][rJ] == 2) || (Cells[rI][rJ] == 3))
// TACDeathCounter[rI][rJ]++;
Cells[rI][rJ] = 4; // make necrotic
stemBirthCounter[rI][rJ] = 0;
deaths++;
}
// healthy division
else if ((cell == 0) && (vacantSites(rI, rJ) > 0)) {
if (proliferation[cell]
>= random.nextFloat()) { // If tossing the coin we are to proliferate...
// if (Oxygen[rI][rJ]>prolifThreshold) { // AND the oxygen concentration is enough for
// division..
// consumption[rI][rJ]=consumptionDivision[Cells[rI][rJ]];
int[] daughter = findEmptySite(rI, rJ);
births++;
Cells[daughter[0]][daughter[1]] = 0;
carriedmutation[daughter[0]][daughter[1]] = 0;
carriedGenome[daughter[0]][daughter[1]] =
initGenome; // resetting space to healthy cell with no mutations
}
}
// }
// cancer division
else if ((vacantSitesCancer(rI, rJ) > 0) && (cell > 0))
if (proliferation[cell]
>= random.nextFloat()) { // If tossing the coin we are to proliferate...
if ((cell == 1)
|| ((cell == 2)
&& (Age[rI][rJ] < maxProDivisions))) { // AND the cell is stem or TAC ...
// if (Oxygen[rI][rJ]>prolifThreshold) { // AND the oxygen concentration is enough for
// division..
// consumption[rI][rJ]=consumptionDivision[Cells[rI][rJ]];
int[] daughter = findEmptySiteCancer(rI, rJ); // and there is space (for cancer)
// if ((daughter[0]==0) || (daughter[0]==size) ||
// (daughter[1]==0)||(daughter[1]==size)) {simulationFinished=true;} // stop sim if a
// cell hits the edge
births++;
if (cell == 1) { // stem cell
stemBirthsTotal[rI][rJ]++;
stemBirthCounter[rI][rJ]++;
if (asymmetricRatio > random.nextFloat()) {
Cells[daughter[0]][daughter[1]] = 1; // placing the stem daughter
stemBirthCounter[daughter[0]][daughter[1]] =
stemBirthCounter[rI][rJ]; // update stem birth counter
carriedmutation[daughter[0]][daughter[1]] =
carriedmutation[rI][rJ]; // inherit mutational status of parent
carriedGenome[daughter[0]][daughter[1]] =
carriedGenome[rI][rJ]; // inherit mutational status of parent
if (mutfreq > random.nextFloat()) { // small chance of mutation
mutationNum++; // advance mutation number
System.out.println(
+carriedmutation[rI][rJ]
+ ", "
+ mutationNum
+ ", "
+ stem_cells_this_TS
+ ", "
+ non_stem_cells_this_TS
+ ", "
+ timestep); // print (parent,child) pair
// tree.put(carriedmutation[rI][rJ], mutationNum);
// timeTree.put(mutationNum, timestep); // hash table stuff
if (0.5 > random.nextFloat()) {
carriedmutation[daughter[0]][daughter[1]] = mutationNum;
genomeToMod = new StringBuilder(carriedGenome[daughter[0]][daughter[1]]);
genomeToMod.setCharAt(
mutationNum - 1, '1'); // daughter carries new carriedGenome
carriedGenome[daughter[0]][daughter[1]] = genomeToMod;
// System.out.println (carriedGenome[rI][rJ]);
// System.out.println (carriedGenome[daughter[0]][daughter[1]]);
} // 50:50 mutate new position daughter
else {
carriedmutation[rI][rJ] = mutationNum; // else mutate original position daughter
genomeToMod = new StringBuilder(carriedGenome[rI][rJ]);
// genomeToMod = carriedGenome[rI][rJ];
carriedGenome[rI][rJ] = genomeToMod;
genomeToMod.setCharAt(
mutationNum - 1, '1'); // original carries new carriedGenome
// System.out.println (carriedGenome[rI][rJ]);
// System.out.println (carriedGenome[daughter[0]][daughter[1]]);
}
}
} else {
Cells[daughter[0]][daughter[1]] = 2; // asymmetric division, daughter is TAC
stemBirthCounter[daughter[0]][daughter[1]] = 0; // reset stem counter
carriedmutation[daughter[0]][daughter[1]] =
carriedmutation[rI][rJ]; // TAC carries parental mutation flag
carriedGenome[daughter[0]][daughter[1]] = carriedGenome[rI][rJ];
} // TAC carries parental genome
// } // redundant from above
// else { // Only if there's hypoxia induced change of symmetric division ratio
// float newASR=asymmetricRatio+0*(hypoxia-Oxygen[rI][rJ]);
// currently OFF by way of 0 the ^^ multiplier.
// if (newASR>random.nextFloat())
// {Cells[daughter[0]][daughter[1]]=1;stemBirthCounter[daughter[0]][daughter[1]]=stemBirthCounter[rI][rJ];}
// else
// {Cells[daughter[0]][daughter[1]]=2;stemBirthCounter[daughter[0]][daughter[1]]=0;}
// // Otherwise differentiate
// }
} else if (cell == 2) { // non-stem division
// TACBirthCounter[rI][rJ]++;
if (Age[rI][rJ] < maxProDivisions - 1) {
Cells[daughter[0]][daughter[1]] = 2;
Age[rI][rJ]++;
Age[daughter[0]][daughter[1]] = Age[rI][rJ];
carriedmutation[daughter[0]][daughter[1]] =
carriedmutation[rI][rJ]; // TAC carries parental mutation flag
carriedGenome[daughter[0]][daughter[1]] =
carriedGenome[rI][rJ]; // TAC carries parental genome
} else {
Cells[daughter[0]][daughter[1]] = 3;
Cells[rI][rJ] = 3;
Age[rI][rJ] = 0;
Age[daughter[0]][daughter[1]] = Age[rI][rJ];
carriedmutation[daughter[0]][daughter[1]] =
carriedmutation[rI][rJ]; // TAC carries parental mutation flag
carriedGenome[daughter[0]][daughter[1]] =
carriedGenome[rI][rJ]; // TAC carries parental genome
}
}
}
} else if (pMotility > random.nextFloat()) { // Migration = not in use
int[] daughter = findEmptySite(rI, rJ);
Cells[daughter[0]][daughter[1]] = cell;
Cells[rI][rJ] = 0;
Age[daughter[0]][daughter[1]] = Age[rI][rJ];
Age[rI][rJ] = 0;
System.err.println("moving " + rI + ", " + rJ);
}
// Aging for mature cells
if (cell == 3) Age[rI][rJ]++;
}
return true;
}
