/// <summary>
/// Method for mutation
/// </summary>
private void mutate(List <string> Individual, int IndividualIdx, ORF orf)
{
int codonIdx = rnd.Next(0, Individual.Count() - 1);
string amino = SeqParser.codonToAmino[Individual[codonIdx]];
// replacing randomized codon and recalculating of score
Individual[codonIdx] = randomizeCodon(amino);
//Homopolymers Removal
if (AHomopolymersRemoval == true)
{
HomopolymersRemove(Individual);
}
if (MaintainOriginalNc == true)
{
if (OptimizationMode == 1)
{
PopulationScores[IndividualIdx] = ORF.MultiScore(Population[IndividualIdx], orf.aminoAcidCounts, minimalNc, maximalNc, 1);
}
if (OptimizationMode == 0)
{
PopulationScores[IndividualIdx] = ORF.MultiScore(Population[IndividualIdx], orf.aminoAcidCounts, minimalNc, maximalNc, 0);
}
}
else
{
PopulationScores[IndividualIdx] = ORF.CPBcalculator(Population[IndividualIdx]);
}
}
public ORF(ORF orfToCopy)
{
orfSeq = new List <string>(orfToCopy.orfSeq);
aminoORFseq = new List <string>(orfToCopy.aminoORFseq);
}
/// <summary>
/// ORF optimization
/// </summary>
/// <param name="ORFSeq"></param>
/// <param name="AminoORFseq"></param>
/// <param name="optimizationMode"></param>
/// <returns></returns>
public List <string> optimizeORF(ORF orf, object o, DoWorkEventArgs e)
{
int stopCounter = 0;
double lastScore = 0;
bool allowed;
// new population and new scores initialization
NewPopulation = new List <List <string> >();
NewPopulationScores = new List <double>();
minimalNc = MinimalNc;
maximalNc = MaximalNc;
// preparation
// codons grouping to dictionary
codonGroups = new Dictionary <string, List <string> >();
codonGroups = SeqParser.codonToAmino.GroupBy(x => x.Value)
.ToDictionary(x => x.Key, x => x.Select(i => i.Key).ToList());
//calculation of minimal and maximal Nc
if (MaintainOriginalNc == true)
{
minimalNc = ORF.NcCalculator(orf.orfSeq, orf.aminoAcidCounts) - minimalNc;
maximalNc = ORF.NcCalculator(orf.orfSeq, orf.aminoAcidCounts) + maximalNc;
}
//Homopolymers counting
if (AHomopolymersRemoval == true)
{
lysineIdx = HomopolymersCheck(orf.aminoORFseq);
}
// initial population generation
generateInitialPopulation(orf);
//Restriction enzymes sites removal
if (RestrEnzymeSitesToRemoval == true)
{
allowed = false;
for (int i = 0; i < PopulationSize; i++)
{
while (allowed == false)
{
allowed = enzymeSitesRemove(Population[i], allowed, i);
}
}
}
//Homopolymers removal
if (AHomopolymersRemoval == true)
{
for (int i = 0; i < PopulationSize; i++)
{
HomopolymersRemove(Population[i]);
}
if (RestrEnzymeSitesToRemoval == true)
{
for (int i = 0; i < PopulationSize; i++)
{
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(Population[i], allowed, i);
}
}
}
}
if (AHomopolymersRemoval == true || RestrEnzymeSitesToRemoval == true)
{
PopulationScores.Clear();
for (int i = 0; i < PopulationSize; i++)
{
if (OptimizationMode == 1)
{
PopulationScores.Add(ORF.MultiScore(orf.orfSeq, orf.aminoAcidCounts, minimalNc, maximalNc, 1));
}
if (OptimizationMode == 0)
{
PopulationScores.Add(ORF.MultiScore(orf.orfSeq, orf.aminoAcidCounts, minimalNc, maximalNc, 0));
}
}
}
// reproductive cycles
for (int i = 0; i < ReproductiveCyclesNumber; i++)
{
// mutation
for (int j = 0; j < Math.Round(Population.Count * MutationProbability); j++)
{
// individual randomization
int individual = rnd.Next(0, Population.Count());
// mutation of given codon
mutate(Population[individual], individual, orf);
}
if (CrossoverProbability != 0)
{
// selection
selectIndividualsForCrossover(TournamentSize);
// crossover
crossover(orf, minimalNc, maximalNc);
if (lastScore != BestScore)
{
lastScore = BestScore;
stopCounter = 0;
}
else
{
stopCounter++;
}
if (stopCounter == StopCriterion)
{
i = ReproductiveCyclesNumber - 1;
}
}
Thread.Sleep(1);
(o as BackgroundWorker).ReportProgress(100 * i / (ReproductiveCyclesNumber - 1));
}
// updating best individual
updateBestIndividual();
return(BestIndividual);
}
/// <summary>
/// Method for crossover (uniform crossover)
/// </summary>
private void crossover(ORF orf, double minimalNc, double maximalNc)
{
// temporary variables
// first parent and second parent indexes
int FirstParentIdx, SecondParentIdx;
// new individuals
List <string> FirstNewIndividual, SecondNewIndividual;
// crossover mask
List <int> CrossoverMask;
int CrossoverMaskSize = Population[0].Count();
//clearing new population and scores
NewPopulation.Clear();
NewPopulationScores.Clear();
int end;
bool allowed;
if (Math.Round(PopulationSize * CrossoverProbability) % 2 != 0)
{
end = PopulationSize - (int)Math.Round(PopulationSize * CrossoverProbability) + 1;
}
else
{
end = PopulationSize - (int)Math.Round(PopulationSize * CrossoverProbability);
}
for (int i = 0; i < end; i++)
{
FirstParentIdx = rnd.Next(0, Population.Count());
//Restricion enzymes sites removal
if (RestrEnzymeSitesToRemoval == true)
{
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(Population[FirstParentIdx], allowed, i);
}
}
//Homopolymers removal
if (AHomopolymersRemoval == true)
{
HomopolymersRemove(Population[FirstParentIdx]);
allowed = false;
//Restricion enzymes sites removal
if (RestrEnzymeSitesToRemoval == true)
{
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(Population[FirstParentIdx], allowed, i);
}
}
}
NewPopulation.Add(Population[FirstParentIdx]);
NewPopulationScores.Add(PopulationScores[FirstParentIdx]);
Population.RemoveAt(FirstParentIdx);
PopulationScores.RemoveAt(FirstParentIdx);
}
// randomization of parents for cross over
for (int i = 0; i < (PopulationSize - end) / 2; i++)
{
FirstParentIdx = rnd.Next(0, Population.Count());
SecondParentIdx = rnd.Next(0, Population.Count());
// rerandomization if parent index was repeated
while (FirstParentIdx == SecondParentIdx)
{
SecondParentIdx = rnd.Next(0, Population.Count());
}
// new crossover mask initialization
CrossoverMask = new List <int>();
for (int x = 0; x < CrossoverMaskSize; x++)
{
CrossoverMask.Add(rnd.Next(0, 2));
}
// new individuals initialization
FirstNewIndividual = new List <string>();
SecondNewIndividual = new List <string>();
// creation of new individuals using the crossover mask
for (int x = 0; x < CrossoverMaskSize; x++)
{
if (CrossoverMask[x] == 0)
{
FirstNewIndividual.Add(Population[FirstParentIdx][x]);
SecondNewIndividual.Add(Population[SecondParentIdx][x]);
}
if (CrossoverMask[x] == 1)
{
FirstNewIndividual.Add(Population[SecondParentIdx][x]);
SecondNewIndividual.Add(Population[FirstParentIdx][x]);
}
}
//Restricion enzymes sites removal
if (RestrEnzymeSitesToRemoval == true)
{
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(FirstNewIndividual, allowed, i);
}
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(SecondNewIndividual, allowed, i);
}
}
//Homopolymers removal
if (AHomopolymersRemoval == true)
{
HomopolymersRemove(FirstNewIndividual);
HomopolymersRemove(SecondNewIndividual);
allowed = false;
//Restricion enzymes sites removal
if (RestrEnzymeSitesToRemoval == true)
{
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(FirstNewIndividual, allowed, i);
}
allowed = false;
while (allowed == false)
{
allowed = enzymeSitesRemove(SecondNewIndividual, allowed, i);
}
}
}
if (MaintainOriginalNc == true)
{
// creating new population with new individuals and new scores
NewPopulation.Add(FirstNewIndividual);
NewPopulation.Add(SecondNewIndividual);
if (OptimizationMode == 1)
{
NewPopulationScores.Add(ORF.MultiScore(FirstNewIndividual, orf.aminoAcidCounts, minimalNc, maximalNc, 1));
NewPopulationScores.Add(ORF.MultiScore(SecondNewIndividual, orf.aminoAcidCounts, minimalNc, maximalNc, 1));
}
if (OptimizationMode == 0)
{
NewPopulationScores.Add(ORF.MultiScore(FirstNewIndividual, orf.aminoAcidCounts, minimalNc, maximalNc, 0));
NewPopulationScores.Add(ORF.MultiScore(SecondNewIndividual, orf.aminoAcidCounts, minimalNc, maximalNc, 0));
}
// removing "used" parents
if (FirstParentIdx > SecondParentIdx)
{
Population.RemoveAt(FirstParentIdx);
Population.RemoveAt(SecondParentIdx);
}
else
{
Population.RemoveAt(SecondParentIdx);
Population.RemoveAt(FirstParentIdx);
}
}
else
{
// creating new population with new individuals and new scores
NewPopulation.Add(FirstNewIndividual);
NewPopulation.Add(SecondNewIndividual);
NewPopulationScores.Add(ORF.CPBcalculator(FirstNewIndividual));
NewPopulationScores.Add(ORF.CPBcalculator(SecondNewIndividual));
// removing "used" parents
if (FirstParentIdx > SecondParentIdx)
{
Population.RemoveAt(FirstParentIdx);
Population.RemoveAt(SecondParentIdx);
}
else
{
Population.RemoveAt(SecondParentIdx);
Population.RemoveAt(FirstParentIdx);
}
}
}
PopulationScores.Clear();
for (int j = 0; j < NewPopulation.Count(); j++)
{
Population.Add(NewPopulation[j]);
PopulationScores.Add(NewPopulationScores[j]);
}
// updating best individual
updateBestIndividual();
}
/// <summary>
/// Method for generation of initial population
/// </summary>
/// <param name="AminoORFseq"></param>
private void generateInitialPopulation(ORF orf)
{
// new population of individuals and scores initialization, new best individual initialization
Population = new List <List <string> >();
PopulationScores = new List <double>();
BestIndividual = new List <string>();
// temporary variables
List <string> tempIndividual;
string tempCodon;
if (MaintainOriginalNc != true)
{
for (int i = 0; i < PopulationSize; i++)
{
// new individual initialization
tempIndividual = new List <string>();
// randomization of codons for given amino acid sequence
foreach (string amino in orf.aminoORFseq)
{
if (amino != "/")
{
tempCodon = randomizeCodon(amino);
tempIndividual.Add(tempCodon);
}
else
{
tempIndividual.Add(orf.orfSeq.Last());
}
}
Population.Add(tempIndividual);
for (int j = 0; j < tempIndividual.Count; j++)
{
Console.Write(tempIndividual[j]);
}
PopulationScores.Add(ORF.CPBcalculator(tempIndividual));
BestScore = PopulationScores[0];
foreach (string c in Population[0])
{
BestIndividual.Add(c);
}
updateBestIndividual();
}
}
if (MaintainOriginalNc == true)
{
for (int i = 0; i < PopulationSize; i++)
{
Population.Add(new List <string>(orf.orfSeq));
if (OptimizationMode == 1)
{
PopulationScores.Add(ORF.MultiScore(orf.orfSeq, orf.aminoAcidCounts, minimalNc, maximalNc, 1));
}
if (OptimizationMode == 0)
{
PopulationScores.Add(ORF.MultiScore(orf.orfSeq, orf.aminoAcidCounts, minimalNc, maximalNc, 0));
}
}
for (int i = 0; i < Population.Count(); i++)
{
for (int j = 0; j < 10; j++)
{
// individual randomization
int individual = rnd.Next(0, Population.Count());
mutate(Population[individual], individual, orf);
}
}
BestScore = PopulationScores[0];
foreach (string c in Population[0])
{
BestIndividual.Add(c);
}
updateBestIndividual();
}
}