public double GetRandomP(SnpDataSet dataSet)
{
double minusLogRandonP = 0;
for (int i = 0; i < this.GetHaplotype().Length; i++)
{
if (this.GetHaplotype(i) == 2)
{
minusLogRandonP += -Math.Log10(dataSet.GetMAF(i + this.GetStart()));
}
else
{
minusLogRandonP += -Math.Log10((double)1 - dataSet.GetMAF(i + this.GetStart()));
}
}
return(minusLogRandonP);
}
public double GetRandomModelLikelihood(SnpDataSet dataSet)
{
double minorLikelihood = 0;
double majorLikelihood = 0;
for (int i = 0; i < this.GetSequence().Length; i++)
{
if (this.GetHaplotype(i) == 0)
{
majorLikelihood += (double)1 / (1 - dataSet.GetMAF(i + this.GetStart()));
}
else
{
minorLikelihood += (double)1 / dataSet.GetMAF(i + this.GetStart());
}
}
return((double)Math.Abs(majorLikelihood / (majorLikelihood + minorLikelihood)));
}
public void Coverage(ArrayList rareBlockList, SnpDataSet dataSet)
{
int[] coverage = new int[dataSet.GetSnpCount()];
int total = 0;
foreach (RareBlock rareBlock in rareBlockList)
{
for (int i = rareBlock.start; i <= rareBlock.end; i++)
{
coverage[i] = 1;
}
}
foreach (int i in coverage)
{
if (i == 1)
{
total++;
}
}
Console.WriteLine(total);
}
public void inWindowExtend(ArrayList group, int snpPosition, SnpDataSet dataSet, ArrayList shareWindowListRef)
{
if (snpPosition == this.end) //when it reached the end of the window
{
ShareWindow newShareWindow = new ShareWindow(); //construct a shareWindow object
newShareWindow.windowStart = this;
newShareWindow.windowLast = this;
newShareWindow.group = group;
group.Sort();
shareWindowListRef.Add(newShareWindow); // Add newShareWindow to shareWindow List;
return;
}
ArrayList group0 = new ArrayList(); //store the individuals that the data of this snp is 0
ArrayList group1 = new ArrayList(); //store the individuals that the data of this snp is 1
ArrayList group2 = new ArrayList(); //store the individuals that the data of this snp is 2
foreach (int individual in group)
{
if (dataSet.GetSnp(individual, snpPosition) == 0) // the data is 0
{
group0.Add(individual);
}
else if (dataSet.GetSnp(individual, snpPosition) == 1) //the data is 1
{
group1.Add(individual);
}
else //the data is 2
{
group2.Add(individual);
}
}
if (group2.Count + group1.Count >= 3) // construct a new group if group2+group1>=3
{
ArrayList group12 = new ArrayList();
foreach (int ind in group2) //add group2 and group1 into group21
{
group12.Add(ind);
}
foreach (int ind in group1)
{
group12.Add(ind);
}
//group12.ToArray();
inWindowExtend(group12, snpPosition + 1, dataSet, shareWindowListRef); //use group21 to do the next Extend
}
if (group0.Count + group1.Count >= 3) // construct a new group if group0+group1>=3, similar to last.
{
ArrayList group01 = new ArrayList();
foreach (int ind in group0)
{
group01.Add(ind);
}
foreach (int ind in group1)
{
group01.Add(ind);
}
//group01.ToArray();
inWindowExtend(group01, snpPosition + 1, dataSet, shareWindowListRef); //do the next Extend
}
}
public void Combine(int i, ArrayList rareBlockList, ArrayList combinedBlockList, SnpDataSet dataSet)
{
if (i == rareBlockList.Count - 1)
{
return; //reach the end of the rareBlockList.
}
ArrayList newGroup = new ArrayList();
ArrayList remainGroup = new ArrayList();
bool flag = true;
for (int j = i + 1; j < i + 50 && j < rareBlockList.Count; j++) // find combined block from this block to 100 blocks away.
{
RareBlock block = new RareBlock();
//Console.WriteLine("{0} {1}", i, j);
block = (RareBlock)((RareBlock)rareBlockList[j]).MemberwiseClone();
if (block.GetStart() < this.GetEnd())
{
continue;
}
int m = 0;
int n = 0;
newGroup.Clear();
remainGroup.Clear();
for (m = 0; m < this.GetGroup().Length; m++) //find the intersection of the two group of individuals.
{
if (n == block.GetGroup().Length)
{
remainGroup.Add(this.GetGroup(m));
break;
}
if (this.group[m] == block.GetGroup(n))
{
newGroup.Add(this.group[m]);
n++;
}
else if (this.group[m] > block.GetGroup(n))
{
n++;
m--;
}
else
{
remainGroup.Add(this.GetGroup(m));
}
}
if (newGroup.Count > 2) //more than 1 guys appare in the two rare blocks
{
//Console.Write("{0} {1} {2}\t", i, j, newGroup.Count);
//foreach (int ind in newGroup)
// Console.Write("{0} ",ind);
//Console.WriteLine();
//Console.ReadKey();
RareBlock newRareBlock = new RareBlock();
newRareBlock.SetStart(this.GetStart());
newRareBlock.SetEnd(block.GetEnd());
newRareBlock.SetGroup((int[])newGroup.ToArray(typeof(int)));
if (newRareBlock.CheckCommon(dataSet)) //check the snp data between the rare blocks
//if (true)
{
if (newRareBlock.GetGroup().Length == 3)
{
newRareBlock.Extend(dataSet);
if (newRareBlock.GetEnd() - newRareBlock.GetStart() > 170)
{
if (combinedBlockList.Count > 0)
{
RareBlock lastRareBlock = (RareBlock)((RareBlock)combinedBlockList[combinedBlockList.Count - 1]).MemberwiseClone();
if (!lastRareBlock.CheckSame(this))
{
if (this.CheckContain(lastRareBlock))
{
combinedBlockList[combinedBlockList.Count - 1] = this.GetCopy();
}
else
{
combinedBlockList.Add(this.GetCopy());
}
}
}
else
{
combinedBlockList.Add(this.GetCopy());
}
}
}
else
{
newRareBlock.Combine(j, rareBlockList, combinedBlockList, dataSet);//if pass, continue combining.
}
//break; //When we find another block to combine to this block ,stop searching for this block.
//Time saving a lot, can miss some, discuss later on.
if (this.group.Length - newRareBlock.group.Length == 0)
{
flag = false;
break;
}
//else if (newRareBlock.group.Length / (this.group.Length - newRareBlock.group.Length) >= 3) break;
}
/*
* if (this.group.Length - newRareBlock.group.Length >= 3)
* {
* RareBlock remainGroupBlock = new RareBlock();
* remainGroupBlock.start = this.start;
* remainGroupBlock.end = this.end;
* remainGroupBlock.sequence = this.sequence;
* remainGroupBlock.group = (int[])remainGroup.ToArray(typeof(int));
* remainGroupBlock.Combine(j, rareBlockList, combinedBlockList, dataSet);
* }
*/
}
}
if (flag && (this.GetEnd() - this.GetEnd()) > 70)
{
if (combinedBlockList.Count > 0)
{
RareBlock lastRareBlock = (RareBlock)combinedBlockList[combinedBlockList.Count - 1];
if (!lastRareBlock.CheckSame(this))
{
if (this.CheckContain(lastRareBlock))
{
combinedBlockList[combinedBlockList.Count - 1] = this.GetCopy();
}
else
{
combinedBlockList.Add(this.GetCopy());
}
}
}
else
{
combinedBlockList.Add(this.GetCopy());
}
}
}
public void Extend(SnpDataSet dataSet)
{
int newStart = this.GetStart();
int newEnd = this.GetEnd();
ArrayList newEndingSequence = new ArrayList();
while (newEnd < dataSet.GetSnpCount() - 1)
{
int data = -1;
bool flag = false;
for (int i = 1; i < this.group.Length; i++)
{
if (data == -1)
{
if (dataSet.GetSnp(this.group[i], newEnd + 1) != 1)
{
data = dataSet.GetSnp(this.group[i], newEnd + 1);
}
}
else if (Math.Abs(dataSet.GetSnp(this.group[i], newEnd + 1) - data) == 2)
{
flag = true;
break;
}
}
if (flag)
{
break;
}
if (data == -1)
{
newEndingSequence.Add(1);
}
else if (data == 0)
{
newEndingSequence.Add(0);
}
else
{
newEndingSequence.Add(2);
}
newEnd++;
}
ArrayList newStartingSequence = new ArrayList();
while (newStart > 0)
{
int data = -1;
bool flag = false;
for (int i = 1; i < this.GetGroup().Length; i++)
{
if (data == -1)
{
if (dataSet.GetSnp(this.group[i], newStart - 1) != 1)
{
data = dataSet.GetSnp(this.group[i], newStart - 1);
}
}
else if (Math.Abs(dataSet.GetSnp(this.group[i], newStart - 1) - data) == 2)
{
flag = true;
break;
}
}
if (flag)
{
break;
}
if (data == -1)
{
newStartingSequence.Add(1);
}
else if (data == 0)
{
newStartingSequence.Add(0);
}
else
{
newStartingSequence.Add(2);
}
newStart--;
}
newStartingSequence.Reverse();
int[] newWholeSequence = new int[this.sequence.Length + newStartingSequence.Count + newEndingSequence.Count];
newStartingSequence.CopyTo(newWholeSequence);
this.GetSequence().CopyTo(newWholeSequence, newStartingSequence.Count);
newEndingSequence.CopyTo(newWholeSequence, newStartingSequence.Count + this.sequence.Length);
this.SetSequence(newWholeSequence);
this.SetStart(newStart);
this.SetEnd(newEnd);
if (this.GetEnd() - this.GetEnd() > 170)
{
;
}
while (newEnd < dataSet.GetSnpCount())
{
ArrayList group0 = new ArrayList();
ArrayList group1 = new ArrayList();
ArrayList group2 = new ArrayList();
for (int i = 0; i < this.GetGroup().Length; i++)
{
if (this.GetGroup(i) == 0)
{
group0.Add(this.GetGroup(i));
}
else if (this.GetGroup(i) == 2)
{
group2.Add(this.GetGroup(i));
}
else
{
group1.Add(this.GetGroup(i));
}
}
}
}
private bool CheckCommon(SnpDataSet dataSet) //check snp data between rare blocks
{
int[] error = new int[this.group.Length]; //error data.
this.sequence = new int[this.end - this.start + 1];
for (int e = 0; e < error.Length; e++) // all is 0 at the begining.
{
error[e] = 0;
}
for (int i = start; i < end; i++) //loop from start to end for snp
{
int count0 = 0; //count how many 0
int count2 = 0; //count how many 2
int[] dataTmp = new int[this.group.Length]; //store the data, avoid multi data accessing
//for (int d = 0; d < dataTmp.Length; d++) //
// d = 0;
int j = 0;
foreach (int ind in this.group) // for each guy in group ,check this snp data
{
int data = dataSet.GetSnp(ind, i);
if (data == 2)
{
count2++;
}
else if (data == 0)
{
count0++;
}
dataTmp[j] = data; //store the data.
j++;
}
if (count2 <= count0) //two minor allele is the outlier in the group
{
for (int m = 0; m < this.group.Length; m++)
{
if (dataTmp[m] == 2)
{
error[m]++;
}
}
sequence[i - start] = 0;
}
else //two major allele is the outlier in the group
{
for (int m = 0; m < this.group.Length; m++)
{
if (dataTmp[m] == 0)
{
error[m]++;
}
}
sequence[i - start] = 2;
}
if (count2 == 0 && count0 == 0)
{
sequence[i - start] = 1;
}
}
ArrayList newGroup = new ArrayList();
for (int n = 0; n < this.group.Length; n++)
{
if (!(error[n] > 0)) //no error or little error, keep this guy.
{
newGroup.Add(this.group[n]);
}
}
if (newGroup.Count < 3)
{
return(false);
}
else
{
this.group = (int[])newGroup.ToArray(typeof(int));
return(true);
}
}
public void CaseControlEvaluation(GeneticDistance newGeneticDistance, MapData newMapData, BlockDictionary newBlockDictionary, Commands newCommands, ResultList finalResultList)
{
SnpDataSet caseData = new SnpDataSet(); //Creat Case data set
SnpDataSet controlData = new SnpDataSet(); //Creat Control data set
Console.Write("\tReading ped data...");
Inputdata inputData = new Inputdata();
inputData.data(caseData, controlData, newCommands); //start getting the data and put into case/comtrol set
ArrayList controlIndividualList = new ArrayList();
ArrayList caseIndividualList = new ArrayList();
Console.Write("finished.\n");
inputData = null;
GC.Collect();
Console.Write("Analyzing LD data...");
double[,] controlLinkageData = new double[controlData.GetSnpCount(), 7];
//caseData.Linkage(caseLinkageData);
controlData.SetIndividualList(controlIndividualList);
controlData = null;
GC.Collect();
Console.Write("finished.\n");
finalResultList.SetControlResult(caseData.individual.Length, 0.2);
Console.WriteLine("Haplotyping for all the control samples...");
for (int indIndex = 0; indIndex < controlIndividualList.Count; indIndex++)
{
((Individual)(controlIndividualList[indIndex])).SetIndividualID(indIndex);
}
int ind = 0;
foreach (Individual newIndividual in controlIndividualList) //haplotyping for each individual.
{
newIndividual.Haplotyping(newBlockDictionary, newMapData, controlLinkageData);
ind++;
Console.SetCursorPosition(8, Console.CursorTop);
Console.Write("{0} / {1}", ind, controlIndividualList.Count);
}
Console.Write("\t\tFinished.\n");
for (int n = 0; n < newCommands.permutation; n++) //permutation
{
Console.Write("Iteration: {0} / {1} \n", n + 1, newCommands.permutation);
List <GroupShare> resultList = new List <GroupShare>(); //unfinished result from last window
List <int> selectControlList = new List <int>();
selectControlList = this.Select(controlIndividualList.Count, caseData.individual.Length, new Random());
//selectControlList = this.Select(controlIndividualList.Count, 30, new Random());
for (int windowStart = 0; windowStart <= newBlockDictionary.blockList.Count - 1; windowStart += 30000)
{
List <GroupShare> newResultList = new List <GroupShare>();
int windowEnd = Math.Min(windowStart + 30000, newBlockDictionary.blockList.Count - 1);
ArrayList wholePairwiseIBDRegionList = new ArrayList();
Console.WriteLine("\t\tSearching for pairwise sharing regions");
for (int i = 0; i < selectControlList.Count; i++)
{
for (int j = i + 1; j < selectControlList.Count; j++)
{
((Individual)controlIndividualList[selectControlList[i]]).PairwiseComparison(wholePairwiseIBDRegionList, (Individual)controlIndividualList[selectControlList[j]], (Block[])newBlockDictionary.blockList.ToArray(typeof(Block)), newMapData, newCommands.cut, windowStart, windowEnd);
}
Console.SetCursorPosition(16, Console.CursorTop);
Console.Write("{0} / {1}\tTotal regions: {2}", i + 1, selectControlList.Count, wholePairwiseIBDRegionList.Count);
}
Console.WriteLine("\t\tFinished.");
MyIBDComparer newComparer = new MyIBDComparer();
wholePairwiseIBDRegionList.Sort(newComparer);
GroupShareFinder newIBDList = new GroupShareFinder(wholePairwiseIBDRegionList);
Console.WriteLine("\t\tSrart searching for group sharing regions: ");
newIBDList.findGroupIBD(controlIndividualList, newBlockDictionary, controlLinkageData, newResultList, resultList, windowStart, windowEnd);
finalResultList.AddNewControlList(newResultList, caseData.individual.Length, 0.2);
}
}
Console.WriteLine("Finished permutation in controls");
finalResultList.CalculateControlResultParameters();
Console.WriteLine("Finished puermutation result calculation");
caseData.SetIndividualList(caseIndividualList);
caseData = null;
GC.Collect();
Console.WriteLine("Haplotyping for all case samples...");
for (int indIndex = 0; indIndex < caseIndividualList.Count; indIndex++)
{
((Individual)(caseIndividualList[indIndex])).SetIndividualID(indIndex);
}
ind = 0;
foreach (Individual newIndividual in caseIndividualList) //haplotyping for each individual.
{
newIndividual.Haplotyping(newBlockDictionary, newMapData, controlLinkageData);
ind++;
Console.SetCursorPosition(8, Console.CursorTop);
Console.Write("{0} / {1}", ind, caseIndividualList.Count);
}
Console.Write("\t\tFinished.\n");
for (int n = 0; n < 1; n++) //case evaluation
{
Console.Write("\tTotally {0} blocks will be analyzed.\n", newBlockDictionary.blockList.Count);
List <GroupShare> resultList = new List <GroupShare>(); //unfinished result from last window
for (int windowStart = 0; windowStart <= newBlockDictionary.blockList.Count - 1; windowStart += 30000)
{
List <GroupShare> newResultList = new List <GroupShare>();
int windowEnd = Math.Min(windowStart + 30000, newBlockDictionary.blockList.Count - 1);
Console.WriteLine("\tAnalyzing block {0} to {1}", windowStart, windowEnd - 1);
ArrayList wholePairwiseIBDRegionList = new ArrayList();
Console.WriteLine("\t\tSearching for pairwise sharing regions");
for (int i = 0; i < caseIndividualList.Count; i++)
{
for (int j = i + 1; j < caseIndividualList.Count; j++)
{
((Individual)caseIndividualList[i]).PairwiseComparison(wholePairwiseIBDRegionList, (Individual)caseIndividualList[j], (Block[])newBlockDictionary.blockList.ToArray(typeof(Block)), newMapData, newCommands.cut, windowStart, windowEnd);
}
Console.SetCursorPosition(16, Console.CursorTop);
Console.Write("{0} / {1}\tTotal regions: {2}", i + 1, caseIndividualList.Count, wholePairwiseIBDRegionList.Count);
}
Console.WriteLine("\n\t\tFinished searching pairwise sharing regions");
MyIBDComparer newComparer = new MyIBDComparer();
wholePairwiseIBDRegionList.Sort(newComparer);
GroupShareFinder newIBDList = new GroupShareFinder(wholePairwiseIBDRegionList);
Console.WriteLine("\t\tSrart searching for group sharing regions:");
newIBDList.findGroupIBD(caseIndividualList, newBlockDictionary, controlLinkageData, newResultList, resultList, windowStart, windowEnd);
finalResultList.calculateAllPvalue(newResultList, caseIndividualList.Count, 0.2, newCommands);
finalResultList.Combine(newResultList);
finalResultList.ClearReplication();
}
}
finalResultList.PrintResult(newBlockDictionary, caseIndividualList.Count, 0.2, newCommands);
}
public void data(SnpDataSet caseDataSet, SnpDataSet controlDataSet, Commands newCommands)
{
string strLine;
string[] strArray;
char[] splitArray = new char[] { ' ' };
string[] individualName;
ArrayList collectionArray;
try
{
populationSize = 0;
collectionArray = new ArrayList();
FileStream aFile = new FileStream(newCommands.pedName, FileMode.OpenOrCreate);
StreamReader sr = new StreamReader(aFile);
strLine = sr.ReadLine();
strArray = strLine.Split(splitArray);
Tem = strArray.Length;
while (strLine != null)
{
populationSize++;
strArray = strLine.Split(splitArray);
if (strArray[5] == "2")
{
caseSize++;
}
else
{
controlSize++;
}
collectionArray.Add(strLine);
strLine = sr.ReadLine();
}
sr.Close();
SetAlleleMap(newCommands);
individualName = new string[populationSize];
finalData = new String[populationSize, Tem - 5];
for (int u = 0; u < collectionArray.Count; u++)
{
String R = (String)collectionArray[u];
strArray = R.Split(splitArray);
individualName[u] = strArray[1];
for (int s = 0; s < Tem - 5; s++)
{
finalData[u, s] = strArray[s + 5];
}
}
}
catch (IOException e)
{
Console.WriteLine("An IO exception has been thrown!");
Console.WriteLine(e.ToString());
Console.ReadLine();
return;
}
int[,] TransTab = new int[populationSize, Tem - 5];
rareallel = new int[populationSize, ((Tem - 6) / 2 + 1)];
for (int x = 0; x < populationSize; x++)
{
rareallel[x, 0] = (int)finalData[x, 0][0] - 48;
}
for (int m = 1; m < Tem - 6; m = m + 2)
{
for (int x = 0; x < populationSize; x++)
{
if (finalData[x, m][0] == Convert.ToChar(this.alleleMap[(m - 1) / 2, 0]))
{
TransTab[x, m] = 1;
}
else
{
TransTab[x, m] = 0;
}
if (finalData[x, m + 1][0] == Convert.ToChar(this.alleleMap[(m - 1) / 2, 0]))
{
TransTab[x, m + 1] = 1;
}
else
{
TransTab[x, m + 1] = 0;
}
if (finalData[x, m][0] == Convert.ToChar("0"))
{
TransTab[x, m] = 1;
TransTab[x, m + 1] = 0;
}
rareallel[x, (m + 1) / 2] = TransTab[x, m] + TransTab[x, m + 1];
}
}
controlData = new int[controlSize, (Tem - 6) / 2];
caseData = new int[caseSize, (Tem - 6) / 2];
ArrayList caseIndividualName = new ArrayList();
ArrayList controlIndividualName = new ArrayList();
ArrayList caseIndividualId = new ArrayList();
ArrayList controlIndividualId = new ArrayList();
int casePtr = 0;
int controlPtr = 0;
for (int u = 0; u < populationSize; u++)
{
if (rareallel[u, 0] == 1)
{
controlIndividualName.Add(individualName[u]);
controlIndividualId.Add(u);
String S = (String)collectionArray[u];
for (int m = 1; m <= (Tem - 6) / 2; m++)
{
controlData[controlPtr, m - 1] = rareallel[u, m];
}
controlPtr++;
}
else if (rareallel[u, 0] == 2)
{
caseIndividualName.Add(individualName[u]);
caseIndividualId.Add(u);
String S = (String)collectionArray[u];
for (int m = 1; m <= (Tem - 6) / 2; m++)
{
caseData[casePtr, m - 1] = rareallel[u, m];
}
casePtr++;
}
}
caseDataSet.SetSnp(caseData);
caseDataSet.SetIndividualName((string[])caseIndividualName.ToArray(typeof(string)));
caseDataSet.SetIndividual((int[])caseIndividualId.ToArray(typeof(int)));
caseDataSet.SetSnpCount((Tem - 6) / 2);
controlDataSet.SetSnp(controlData);
controlDataSet.SetIndividualName((string[])controlIndividualName.ToArray(typeof(string)));
controlDataSet.SetIndividual((int[])controlIndividualId.ToArray(typeof(int)));
controlDataSet.SetSnpCount((Tem - 6) / 2);
}
