size_t CExperimentSet::keyToIndex(const std::string & key) const
{
const CExperiment * pExp = dynamic_cast<const CExperiment *>(CRootContainer::getKeyFactory()->get(key));
if (!pExp) return C_INVALID_INDEX;
size_t i, imax = size();
for (i = 0; i < imax; i++)
if (pExp == getExperiment(i)) return i;
return C_INVALID_INDEX;
}
/**
* @brief Run the analysis.
*/
void CNAnalysisMethodMosaicism::run()
{
Verbose::out(1, "CNAnalysisMethodMosaicism::run(...) start");
isSetup();
determineLocalProbeSets();
m_vSegments.deleteAll();
vector<int> vChromosomes = getChromosomes(getProbeSets());
int iLastChromosome = vChromosomes[vChromosomes.size() - 1];
Verbose::progressBegin(1,"CNAnalysisMethodMosaicism::run(...) ", iLastChromosome, 1, iLastChromosome);
for (int i = 0; (i < vChromosomes.size()); i++)
{
int iChromosome = vChromosomes[i];
if (iChromosome == 255) {continue;}
if (iChromosome == m_iYChromosome && !m_bRunYChromosome) {
continue;
}
int iProbeSetCount = getProbeSetCount(iChromosome, getProbeSets());
if (iProbeSetCount == 0) continue; // probably 23 or Y
Verbose::progressStep(1);
// debug: for later use
m_current_experiment=getExperiment()->getExperimentName();
m_current_chr=ToStr(vChromosomes[i]);
std::vector<int> vPositions(iProbeSetCount);
double* pLog2Ratios = new double[iProbeSetCount];
int iStartChromosome = getChrBounds(iChromosome, getProbeSets()).first;
m_iStartIndex = 0;
m_iEndIndex = (iProbeSetCount - 1);
CNProbeSetArray* psets = getProbeSets();
for (int j = 0; (j < iProbeSetCount); j++)
{
vPositions[j] = psets->at(iStartChromosome + j)->getPosition();
pLog2Ratios[j] = psets->at(iStartChromosome + j)->getLog2Ratio();
}
double* pRunMean = new double[iProbeSetCount];
int iMarkerBandwidth = Min(iProbeSetCount, m_iMarkerBandwidth);
runmean(pLog2Ratios, pRunMean, &iProbeSetCount, &iMarkerBandwidth);
// debug - this has been ruled out.
#ifdef MOSAICISM_DEBUG_MEANS
writeRunningMeans(m_current_experiment+".chr"+m_current_chr+".means.tsv",
iProbeSetCount,
pLog2Ratios,
pRunMean);
#endif
CNSegmentArray vSegments;
newSegments((unsigned char)iChromosome, pRunMean, iProbeSetCount, vPositions, vSegments);
// dont need this anymore.
delete[] pRunMean;
// debug
#ifdef MOSAICISM_DEBUG
vSegments.writeToTsv(m_current_experiment+"-chr"+m_current_chr+".newseg1.tsv");
#endif
//
cleanSegments(vSegments);
// Set marker count and median marker distance.
for (int iSegmentIndex = 0; (iSegmentIndex < vSegments.getCount()); iSegmentIndex++)
{
CNSegment* p = vSegments.getAt(iSegmentIndex);
p->setStartPosition(vPositions[p->getStartIndex()]);
p->setEndPosition(vPositions[p->getEndIndex()]);
calculateSegmentConfidence(pLog2Ratios, p);
int iMarkerCount = 0;
for (unsigned int iProbeSetIndex = 0; (iProbeSetIndex < vPositions.size()); iProbeSetIndex++)
{
if ((vPositions[iProbeSetIndex] >= p->getStartPosition()) && (vPositions[iProbeSetIndex] <= p->getEndPosition()))
{
iMarkerCount++;
}
}
if (iMarkerCount < 2)
{
p->setMarkerCount(iMarkerCount);
p->setMeanMarkerDistance(0);
}
else
{
AffxMultiDimensionalArray<int> vMarkerDistances(iMarkerCount - 1);
int iIndex = 0;
for (unsigned int iProbeSetIndex = 1; (iProbeSetIndex < vPositions.size()); iProbeSetIndex++)
{
int iPrevPosition = vPositions[iProbeSetIndex - 1];
int iNextPosition = vPositions[iProbeSetIndex];
if ((iPrevPosition >= p->getStartPosition()) && (iNextPosition <= p->getEndPosition()))
{
getProbeSets()->getAt(iStartChromosome + iProbeSetIndex - 1)->setMosaicismMixture(p->getMixtureAsDouble());
getProbeSets()->getAt(iStartChromosome + iProbeSetIndex)->setMosaicismMixture(p->getMixtureAsDouble());
vMarkerDistances.set(iIndex, (iNextPosition - iPrevPosition));
iIndex++;
}
}
p->setMarkerCount(iMarkerCount);
p->setMeanMarkerDistance(vMarkerDistances.mean());
}
// transfer of ownership from vSegments to m_vSegments
m_vSegments.add(p);
}
#ifdef MOSAICISM_DEBUG
vSegments.writeToTsv(m_current_experiment+"-chr"+m_current_chr+".seg2.tsv");
#endif
// why "nullAll()" instead of "deleteAll()"?
// because the pointers were copied to m_vSegments above and
// AffxArray will delete the pointers in vSegments when it goes out of scope.
vSegments.nullAll();
delete[] pLog2Ratios;
}
Verbose::progressEnd(1, "Done");
Verbose::out(1, "CNAnalysisMethodMosaicism::run(...) end");
}
const CMatrix< C_FLOAT64 > & CExperimentSet::getDependentData(const size_t & index) const
{return getExperiment(index)->getDependentData();}
const CTaskEnum::Task & CExperimentSet::getExperimentType(const size_t & index) const
{return getExperiment(index)->getExperimentType();}
/**
* @brief Create new segments
* @param int - The segment type to create
* @param CNSegmentArray& - The segment vector to load
* @param int - The affx sex code
* @param int - The X chromosome numeric value
* @param int - The Y chromosome numeric value
* @return int - The number of new segments created
*/
int CNAnalysisMethodSegment::newSegments( int iSegmentType,
CNProbeSetArray* vProbeSets,
int iMinSegSeparation )
{
AffxMultiDimensionalArray<int> vMarkerDistances(vProbeSets->getCount());
int iPrevMarkerPosition = 0;
if (vProbeSets->getCount() == 0) {return 0;}
int iSegmentCount = 0;
int iMarkerCount = 0;
double dSumConfidence = 0.0;
double dConfidence=0.0;
int iHetsInSegment=0;
int iHomsInSegment=0;
CNSegment* pobjSegment = NULL;
CNProbeSet* pobjProbeSet = NULL;
int iStartIndex = 0;
// If Segment type loh-segment, loh-cyto2, cn-neutral-log, normal-diploid
if ((iSegmentType == 2) || (iSegmentType == 3) || (iSegmentType == 4) || (iSegmentType == 5))
{
for (;(iStartIndex < vProbeSets->getCount()); iStartIndex++)
{
pobjProbeSet = vProbeSets->getAt(iStartIndex);
if ((double)pobjProbeSet->getLoh() == (double)pobjProbeSet->getLoh()) // Not = NaN
{
break;
}
}
}
int iCurrCNState = -1;
bool cytoScanHD = m_pEngine->getOptBool("cytoscan-hd");
if (iStartIndex < vProbeSets->getCount())
{
pobjProbeSet = vProbeSets->getAt(iStartIndex);
if (cytoScanHD)
{
// Case 1: SNP marker with CN=-1 sits at the beginning of the chromosome
unsigned char currentChromosome = pobjProbeSet->getChromosome();
for (int iIndex = iStartIndex; (iIndex < vProbeSets->getCount()); iIndex++)
{
if (currentChromosome != vProbeSets->getAt(iIndex)->getChromosome()) break;
if (vProbeSets->getAt(iIndex)->getCNState() != -1)
{
iCurrCNState = vProbeSets->getAt(iIndex)->getCNState();
break;
}
}
}
char cCall = pobjProbeSet->getSegmentTypeCall(iSegmentType, getExperiment()->getCNCallGenderAsInt(), m_iXChromosome, m_iYChromosome);
float fConfidence = pobjProbeSet->getSegmentTypeConfidence(iSegmentType);
bool bPar = pobjProbeSet->isPseudoAutosomalRegion();
if (cytoScanHD)
{
// Override cCall in the two cases where CN state makes a difference.
if (iSegmentType == 4) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 1)) ? (char)1 : (char)0); // CNNeutralLOH
if (iSegmentType == 5) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 0)) ? (char)1 : (char)0); // Normal Diploid
}
pobjSegment = new CNSegment;
pobjSegment->setSegmentType(iSegmentType);
pobjSegment->setChromosome(pobjProbeSet->getChromosome());
pobjSegment->setStartPosition(pobjProbeSet->getPosition());
pobjSegment->setEndPosition(pobjProbeSet->getPosition());
pobjSegment->setCall(cCall);
pobjSegment->setConfidence((float)0.5);
pobjSegment->setPseudoAutosomalRegion(bPar);
iMarkerCount = 0;
dSumConfidence = 0;
iPrevMarkerPosition = pobjProbeSet->getPosition();
for (int iIndex = iStartIndex; (iIndex < vProbeSets->getCount()); iIndex++)
{
pobjProbeSet = vProbeSets->getAt(iIndex);
cCall = pobjProbeSet->getSegmentTypeCall(iSegmentType, getExperiment()->getCNCallGenderAsInt(), m_iXChromosome, m_iYChromosome);
fConfidence = pobjProbeSet->getSegmentTypeConfidence(iSegmentType);
bPar = pobjProbeSet->isPseudoAutosomalRegion();
// Case 2: If a SNP marker falls within a CN segment (including CN or SNP), assign SNP marker with the same CN state
// Case 3: If a SNP marker falls outside any CN segment, assign CN state for this SNP marker based on the CN segment just right before it.
if (pobjProbeSet->getCNState() != -1) {iCurrCNState = pobjProbeSet->getCNState();}
if (cytoScanHD)
{
// Override cCall in the two cases where CN state makes a difference.
if (iSegmentType == 4) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 1)) ? (char)1 : (char)0); // CNNeutralLOH
if (iSegmentType == 5) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 0)) ? (char)1 : (char)0); // Normal Diploid
}
if ((iSegmentType == 2) || (iSegmentType == 3) || (iSegmentType == 4) || (iSegmentType == 5))
{
if ((double)pobjProbeSet->getLoh() != (double)pobjProbeSet->getLoh()) // NaN
{
continue;
}
}
bool newSegmentTestFlag = false;
if(iSegmentType == 2)
{
newSegmentTestFlag = (
(pobjProbeSet->getChromosome() != pobjSegment->getChromosome())
|| (cCall != pobjSegment->getCall())
|| ((getExperiment()->getCNCallGenderAsInt() == affx::Male) && (iSegmentType == 1) && (bPar != pobjSegment->isPseudoAutosomalRegion()))
|| (fabs((float)iPrevMarkerPosition - (float) (pobjProbeSet->getPosition())) > (float) iMinSegSeparation)
);
}
else
{
newSegmentTestFlag = (
(pobjProbeSet->getChromosome() != pobjSegment->getChromosome())
|| (cCall != pobjSegment->getCall())
|| ((getExperiment()->getCNCallGenderAsInt() == affx::Male) && (iSegmentType == 1) && (bPar != pobjSegment->isPseudoAutosomalRegion()))
);
}
if (newSegmentTestFlag)
{
pobjSegment->setMeanMarkerDistance((float)vMarkerDistances.mean(iMarkerCount - 1));
pobjSegment->setSegmentName(affxutil::Guid::GenerateNewGuid());
pobjSegment->setMarkerCount(iMarkerCount);
pobjSegment->setConfidence((float)(dSumConfidence / (double)iMarkerCount));
if(cytoScanHD)
{
if(iSegmentType==2)
{
dConfidence = assignConfidenceSigmoidal( iHetsInSegment,
iHetsInSegment + iHomsInSegment,
getExperiment()->getHetFrequency(),
getExperiment()->getPError(),
3,
10);
pobjSegment->setConfidence((float) dConfidence);
}
if(iSegmentType==4)
{
dConfidence = assignConfidenceSigmoidal( iHetsInSegment,
iHetsInSegment + iHomsInSegment,
getExperiment()->getHetFrequency(),
getExperiment()->getPError(),
3,
10);
pobjSegment->setConfidence((float) (dConfidence/2.0));
}
}
m_vSegments.add(pobjSegment);
iSegmentCount++;
if (cytoScanHD && pobjProbeSet->getChromosome() != pobjSegment->getChromosome())
{
// Case 1: SNP marker with CN=-1 sits at the beginning of the chromosome
iCurrCNState = -1;
unsigned char currentChromosome = pobjProbeSet->getChromosome();
for (int iInner = iIndex; (iInner < vProbeSets->getCount()); iInner++)
{
if (currentChromosome != vProbeSets->getAt(iIndex)->getChromosome()) break;
if (vProbeSets->getAt(iInner)->getCNState() != -1)
{
iCurrCNState = vProbeSets->getAt(iInner)->getCNState();
break;
}
}
// Override cCall in the two cases where CN state makes a difference.
if (iSegmentType == 4) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 1)) ? (char)1 : (char)0); // CNNeutralLOH
if (iSegmentType == 5) cCall = (((iCurrCNState == 2) && (pobjProbeSet->getLoh() == 0)) ? (char)1 : (char)0); // Normal Diploid
}
pobjSegment = new CNSegment;
pobjSegment->setSegmentType(iSegmentType);
pobjSegment->setChromosome(pobjProbeSet->getChromosome());
pobjSegment->setStartPosition(pobjProbeSet->getPosition());
pobjSegment->setCall(cCall);
pobjSegment->setConfidence((float)0.5);
pobjSegment->setPseudoAutosomalRegion(bPar);
iHetsInSegment=0;
iHomsInSegment=0;
iMarkerCount = 0;
dSumConfidence = 0;
iPrevMarkerPosition = pobjProbeSet->getPosition();
}
iMarkerCount++;
if(pobjProbeSet->getGenotypeCall() == (char) 2 || pobjProbeSet->getGenotypeCall() == (char) 0)
{
iHomsInSegment++;
}
if(pobjProbeSet->getGenotypeCall() == (char) 1 )
{
iHetsInSegment++;
}
dSumConfidence += fConfidence;
pobjSegment->setEndPosition(pobjProbeSet->getPosition());
if (iMarkerCount > 1) {vMarkerDistances.set((iMarkerCount - 2), (pobjProbeSet->getPosition() - iPrevMarkerPosition));}
iPrevMarkerPosition = pobjProbeSet->getPosition();
}
}
if (pobjSegment != NULL)
{
pobjSegment->setConfidence((float)(dSumConfidence / (double)iMarkerCount));
if(cytoScanHD)
{
if(iSegmentType==2)
{
dConfidence = assignConfidenceSigmoidal( iHetsInSegment,
iHetsInSegment + iHomsInSegment,
getExperiment()->getHetFrequency(),
getExperiment()->getPError(),
3,
10);
pobjSegment->setConfidence((float) dConfidence);
}
if(iSegmentType==4)
{
dConfidence = assignConfidenceSigmoidal( iHetsInSegment,
iHetsInSegment + iHomsInSegment,
getExperiment()->getHetFrequency(),
getExperiment()->getPError(),
3,
10);
pobjSegment->setConfidence((float) (dConfidence/2.0));
}
}
pobjSegment->setMeanMarkerDistance((float)vMarkerDistances.mean(iMarkerCount - 1));
pobjSegment->setMarkerCount(iMarkerCount);
pobjSegment->setSegmentName(affxutil::Guid::GenerateNewGuid());
m_vSegments.add(pobjSegment); iSegmentCount++;
}
return iSegmentCount;
}
MainWindow::MainWindow(QWidget *parent) :
QMainWindow(parent),
ui(new Ui::MainWindow)
{
QLocale::setDefault(QLocale::English);
//setAttribute(Qt::WA_DeleteOnClose,true);
ui->setupUi(this);
experimentSettings=new QSettings (QSettings::IniFormat,QSettings::UserScope,QApplication::organizationName(),"experiment",this);
experiment=new Experiment();
tcp=new TcpServer(this);
tcp->setExperiment(experiment);
udp=new UdpServer(this);
udp->setExperiment(experiment);
connect(tcp,SIGNAL(warning(QString)),SLOT(warning(QString)));
connect(tcp,SIGNAL(notify(QString)),SLOT(notify(QString)));
//bind tcp socket to local port 25050
tcp->bind(25050);
connect(experiment,SIGNAL(statusChanged(bool)),tcp,SLOT(experimentStatusChanged(bool)));
connect(experiment,SIGNAL(intervalChanged(int)),tcp,SLOT(experimentIntervalChanged(int)));
connect(experiment,SIGNAL(TcpForbidden(QString)),tcp,SLOT(experimentForbidden(QString)));
connect(ui->actionExit,SIGNAL(triggered()),this,SLOT(close()));
connect(ui->actionFullscreen,SIGNAL(triggered(bool)),this,SLOT(setFullscreen(bool)));
connect(ui->actionAbout_Qt,SIGNAL(triggered()),this,SLOT(showAboutQt()));
connect(ui->actionNew_experiment,SIGNAL(triggered()),this,SLOT(getExperiment()));
connect(ui->actionSave,SIGNAL(triggered()),experiment,SLOT(saveFile()));
connect(ui->actionSave_as,SIGNAL(triggered()),this,SLOT(getFile()));
connect(ui->actionStartMeasure,SIGNAL(toggled(bool)),experiment,SLOT(start(bool)));
connect(ui->actionMeasuring_interval,SIGNAL(triggered()),this,SLOT(changeMeasureIntervalDialog()));
connect(ui->actionControls,SIGNAL(triggered()),SLOT(showExperimentControlMangement()));
connect(ui->actionData,SIGNAL(triggered()),SLOT(showData()));
connect(experiment,SIGNAL(statusChanged(bool)),ui->actionStartMeasure,SLOT(setChecked(bool)));
connect(experiment,SIGNAL(statusChanged(bool)),this,SLOT(statusChanged(bool)));
connect(experiment,SIGNAL(experimentChanged(QString)),this,SLOT(setExperiment(QString)));
connect(experiment,SIGNAL(measured(QString)),ui->plainTextEdit,SLOT(appendPlainText(QString)));
connect(experiment,SIGNAL(fileChanged(QString)),this,SLOT(setFile(QString)));
connect(experiment,SIGNAL(Notify(QString)),SLOT(notify(QString)));
connect(experiment,SIGNAL(intervalChanged(int)),SLOT(setMeasureInterval(int)));
connect(experiment,SIGNAL(updateProgress(int)),ui->measureIntervalProgressBar,SLOT(setValue(int)));
connect(tcp,SIGNAL(clientCountChanged(int)),&tcpClientsLabel,SLOT(setNum(int)));
experiment->setInterval(2000);
// Additional ui preparation
experimentLabel.setToolTip("Experiment configuration");
statusLabel.setToolTip("Experiment status:\nR - running\nS - stopped");
QFont font(statusLabel.font());
font.setBold(true);
statusLabel.setFont(font);
//set experiment status to stopped
statusChanged(false);
tcpClientsLabel.setToolTip("Number of tcp clients");
tcpClientsLabel.setNum(0);
statusBar()->addPermanentWidget(&tcpClientsLabel);
statusBar()->addPermanentWidget(&fileLabel);
statusBar()->addPermanentWidget(&experimentLabel);
statusBar()->addPermanentWidget(&statusLabel);
// Ask user to select experiment
getExperiment();
}
/**
* @brief Preprocess the genotype calls to get the marker count cutoff and the het call cutoff
* @param std::vector<char>& - The vector of hom and/or het calls
* @param int& - The marker count cutoff to calculate
* @param int& - The het call cutoff to calculate
* @return bool - Was the function successful or not (true = successful)
*/
bool CNAnalysisMethodLOHCytoScan::lohPreProcessing(std::vector<char>& vHomHet, int& iMarkerCount, int& iHetCutoff)
{
int iHetCount = 0;
int iCallCount = 0;
int iNoCallCount = 0;
double dMaximumGenotypeConfidence = 0;
int iSnpCount = 0;
for (int iIndex = 0; (iIndex < (int)getProbeSets()->size()); iIndex++)
{
CNProbeSet* pobjProbeSet = getProbeSets()->at(iIndex);
pobjProbeSet->setLoh(numeric_limits<float>::quiet_NaN());
if (pobjProbeSet->processAsSNP()) {iSnpCount++;}
vHomHet[iIndex] = pobjProbeSet->getGenotypeCall();
if (vHomHet[iIndex] == (char)2) {vHomHet[iIndex] = (char)0;}
if (pobjProbeSet->getGenotypeConfidence() > m_dLohCNNoCallThreshold) {vHomHet[iIndex] = (char)-1;}
if (vHomHet[iIndex] == 1) {iHetCount++;}
if (vHomHet[iIndex] >= 0)
{
iCallCount++;
dMaximumGenotypeConfidence = Max((float)dMaximumGenotypeConfidence, pobjProbeSet->getGenotypeConfidence());
}
else
{
if (pobjProbeSet->processAsSNP()) {iNoCallCount++;}
}
}
double dErrorRate = m_dLohCNErrorRate;
if (((dMaximumGenotypeConfidence * 1.1) >= m_dLohCNNoCallThreshold) && (m_dLohCNNoCallThreshold == 0.05))
{
dErrorRate = ((double)iNoCallCount / (double)iSnpCount);
dErrorRate = (0.002926 + 6.607106 * dErrorRate);
dErrorRate = ceil(dErrorRate * 100) / 100.0;
if (dErrorRate < m_dLohCNErrorRate) {dErrorRate = m_dLohCNErrorRate;}
}
double dHetRate = ((double)iHetCount / (double) iCallCount);
if (dHetRate > 0.5) {dHetRate = 0.5;}
if (dHetRate < 0.2) {dHetRate = 0.2;}
int iIterations = 1;
int iStart = 20;
int n = 0;
while (iIterations < 3)
{
iHetCutoff = AffxStatistics::binoinv((1 - m_dLohCNAlpha), iStart, dErrorRate);
double a = AffxStatistics::norminv(m_dLohCNBeta);
double sqrtn = (-a * 0.5 * sqrt(1 - dHetRate) / sqrt(dHetRate) + sqrt(a * a * (1 - dHetRate) / (4 * dHetRate) + iHetCutoff / dHetRate));
n = (int)ceil(sqrtn * sqrtn);
if (n == iStart) {break;}
else {iStart = n;}
iIterations++;
}
iMarkerCount = Max(n, m_iLohCNMinimumMarkerCount);
if ((iMarkerCount % 2) == 0) {iMarkerCount++;}
if (iMarkerCount < 3)
{
throw(Except("MarkerCount must be >= 3.")); return false;
}
// The hetRate is used in the CNAnalysisMethodSegment method to assign a confidence to the loh determination. In order
// that this value is accessible there we pass it to the CNExperiment object. Note that the het frequency is also
// computed and stored in a postprocessing function in the CNCytoEngine. The two computations are the same.
// We also need the dErrorRate when calculating confidences. This value is also passed to the experiment object and then accessed
// when segmenting.
getExperiment()->setHetFrequency(dHetRate);
getExperiment()->setPError(dErrorRate);
return true;
}
void CNAnalysisMethodLOHCytoScan::imputeMissingLOHCalls()
{
std::vector<CNProbeSet*> vLOHProbeSets;
for (int iIndex = 0; (iIndex < (int)getProbeSets()->size()); iIndex++)
{
CNProbeSet* pProbeSet = getProbeSets()->getAt(iIndex);
if( pProbeSet->processAsSNP() )
{
vLOHProbeSets.push_back(pProbeSet);
}
}
// This is code to dump out the loh status before the impute algorithm is invoked.
bool testFlag = false;
if(testFlag)
{
affx::TsvFile *tsv = new affx::TsvFile;
tsv->writeTsv(getExperiment()->getExperimentName() + ".LohProbes.txt");
tsv->defineColumn( 0,0,"position", affx::TSV_TYPE_DOUBLE);
tsv->defineColumn( 0,1,"lohState", affx::TSV_TYPE_DOUBLE);
tsv->defineColumn( 0,2,"Chromosome", affx::TSV_TYPE_DOUBLE);
tsv->defineColumn( 0,3,"Genotype", affx::TSV_TYPE_DOUBLE);
for (int iIndex = 0; iIndex < vLOHProbeSets.size(); iIndex++)
{
CNProbeSet* pProbeSet = vLOHProbeSets[iIndex];
tsv->set(0,0,pProbeSet->getPosition());
tsv->set(0,1,pProbeSet->getLoh());
tsv->set(0,2,pProbeSet->getChromosome());
tsv->set(0,3,pProbeSet->getGenotypeCall());
tsv->writeLevel(0);
}
delete tsv;
}
int iLeftIndex=0;
int iRightIndex=1;
int iLeftLohStatus=0;
int iRightLohStatus=0;
CNProbeSet* pLeftProbeSet = NULL;
CNProbeSet* pRightProbeSet = NULL;
while(iRightIndex < vLOHProbeSets.size())
{
pLeftProbeSet = vLOHProbeSets[iLeftIndex];
pRightProbeSet = vLOHProbeSets[iRightIndex];
iLeftLohStatus=pLeftProbeSet->getLoh();
iRightLohStatus=pRightProbeSet->getLoh();
if(!pLeftProbeSet->lohCalled())
{
if(!pRightProbeSet->lohCalled() )
{
// If we don't get an loh call on the right we advance.
iRightIndex++;
// If we have advanced beyond the collection of probesets we clean up since we never get back in the loop.
if(iRightIndex == vLOHProbeSets.size())
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(0);
}
}
continue;
}
else
{
// At this point we have just finished advancing the right pointer and thus 3 things can happen.
// RightIndex passes out of the chromosome or over the centromere.
// Or hits a marker with valid loh call.
// Note that we put the 3rd case last since we can get a valid loh call across a boundary but want to
// deal with it as in the first two cases.
// Note that the right pointer cannot point outside the array since that is the condition on the while loop.
if( (vLOHProbeSets[iRightIndex]->getPosition() - vLOHProbeSets[iRightIndex-1]->getPosition()) > m_iLohCNSeparation)
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(0);
}
// Note that iRightIndex points across a boundary so we do not set it's loh. ie. < not <= in above for loop.
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
// Note that here we can be pointing beyond the array bounds, but even though we never
// get back in the loop we have cleaned up. i.e. set the last set of markers to have non-loh.
continue;
}
if( vLOHProbeSets[iRightIndex]->getChromosome() != vLOHProbeSets[iRightIndex-1]->getChromosome() )
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(0);
}
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
continue;
}
// We now have an loh call on the right but none on the left.
{
for(int iIndex = iLeftIndex; iIndex <= iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(iRightLohStatus);
}
// We now move the left and right indices. Note that how they move depends on whether or not we
// are within a chromsome or if the right index is at the end of a chromsome. In the first case
// we advance the left to the right index since we need this points loh status to continue. In the
// second case we advance both left and right to the first two positions in the next chromsome.
if(iRightIndex+1 == vLOHProbeSets.size())
{
iRightIndex++;
continue;
}
if
(
( vLOHProbeSets[iRightIndex+1]->getChromosome() != vLOHProbeSets[iRightIndex]->getChromosome() )
||
( (vLOHProbeSets[iRightIndex+1]->getPosition()- vLOHProbeSets[iRightIndex]->getPosition()) > m_iLohCNSeparation )
)
{
iLeftIndex=iRightIndex+1;
iRightIndex=iLeftIndex+1;
}
else
{
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
}
continue;
}
}
}
else
{
if(!pRightProbeSet->lohCalled() )
{
iRightIndex++;
if(iRightIndex == vLOHProbeSets.size())
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(iLeftLohStatus);
}
continue;
}
}
else
{
// Again, at this point 3 things can happen.
// RightIndex passes out of the chromosome or over the centromere.
// Or hits a marker with valid loh call.
// Note that we put the 3rd case last since we can get a valid loh call across a boundary but want to
// deal with it as in the first two cases.
if( (vLOHProbeSets[iRightIndex]->getPosition() - vLOHProbeSets[iRightIndex-1]->getPosition()) > m_iLohCNSeparation)
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(iLeftLohStatus);
}
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
// Note that here we can be pointing beyond the array bounds, but even though we never
// get back in the loop we have cleaned up. i.e. set the last set of markers to have non-loh.
continue;
}
if( vLOHProbeSets[iRightIndex]->getChromosome() != vLOHProbeSets[iRightIndex-1]->getChromosome() )
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(iLeftLohStatus);
}
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
continue;
}
// We now have an loh call on the left and the right.
{
// At this point we have 2 cases. The left and right probesets have the same loh state
// Or one has loh the other non-loh.
if(iRightLohStatus==iLeftLohStatus)
{
for(int iIndex = iLeftIndex; iIndex <= iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(iLeftLohStatus);
}
}
else
{
if(iRightLohStatus==0)
{
for(int iIndex = iLeftIndex+1; iIndex <= iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(0);
}
}
else
{
for(int iIndex = iLeftIndex; iIndex < iRightIndex; iIndex++)
{
vLOHProbeSets[iIndex]->setLoh(0);
}
}
}
if(iRightIndex+1 == vLOHProbeSets.size())
{
iRightIndex++;
continue;
}
if
(
( vLOHProbeSets[iRightIndex+1]->getChromosome() != vLOHProbeSets[iRightIndex]->getChromosome() )
||
( (vLOHProbeSets[iRightIndex+1]->getPosition()- vLOHProbeSets[iRightIndex]->getPosition()) > m_iLohCNSeparation )
)
{
iLeftIndex=iRightIndex+1;
iRightIndex=iLeftIndex+1;
}
else
{
iLeftIndex=iRightIndex;
iRightIndex=iLeftIndex+1;
}
continue;
}
}
}
}
}
