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package org.broadinstitute.gatk.utils.pairhmm;
import com.google.java.contract.Ensures;
import com.google.java.contract.Requires;
import org.broadinstitute.gatk.utils.QualityUtils;
import org.broadinstitute.gatk.utils.exceptions.UserException;
import org.broadinstitute.gatk.utils.genotyper.PerReadAlleleLikelihoodMap;
import org.broadinstitute.gatk.utils.genotyper.ReadLikelihoods;
import org.broadinstitute.gatk.utils.haplotype.Haplotype;
import org.broadinstitute.gatk.utils.sam.GATKSAMRecord;
import java.io.BufferedWriter;
import java.io.File;
import java.io.FileWriter;
import java.io.IOException;
import java.util.HashMap;
import java.util.List;
import java.util.Map;
import static org.broadinstitute.gatk.utils.pairhmm.PairHMMModel.*;
/**
* Created with IntelliJ IDEA.
* User: rpoplin, carneiro
* Date: 10/16/12
*/
public class DebugJNILoglessPairHMM extends LoglessPairHMM {
private static final boolean dumpSandboxOnly = false; //simulates ifdef
private static final boolean debug = false; //simulates ifdef
private static final boolean verify = !dumpSandboxOnly && (debug || true); //simulates ifdef
private static final boolean debug0_1 = false; //simulates ifdef
private static final boolean debug1 = false; //simulates ifdef
private static final boolean debug2 = false;
private static final boolean debug3 = false;
//Debugging stats
private int numCalls = 0;
private int numComputeLikelihoodCalls = 0;
protected HashMap<String, BufferedWriter> filenameToWriter = new HashMap<String, BufferedWriter>();
private JNILoglessPairHMM jniPairHMM = null;
public DebugJNILoglessPairHMM(final PairHMM.HMM_IMPLEMENTATION hmmType) {
super();
switch(hmmType) {
case VECTOR_LOGLESS_CACHING:
jniPairHMM = new VectorLoglessPairHMM();
break;
default:
throw new UserException.BadArgumentValue("pairHMM","Specified JNIPairHMM implementation is unrecognized or incompatible with the HaplotypeCaller. Acceptable options are VECTOR_LOGLESS_CACHING");
}
}
@Override
public void close()
{
jniPairHMM.close();
debugClose();
}
//Used only when testing parts of the compute kernel
/**
* {@inheritDoc}
*/
@Override
public void initialize( final int readMaxLength, final int haplotypeMaxLength ) {
if(verify)
super.initialize(readMaxLength, haplotypeMaxLength);
if(debug3)
{
System.out.println("Java: alloc initialized readMaxLength : "+readMaxLength+" haplotypeMaxLength : "+haplotypeMaxLength);
debugDump("lengths_java.txt", String.format("%d %d\n",readMaxLength, haplotypeMaxLength),
true);
}
if(debug2)
jniInitialize(readMaxLength, haplotypeMaxLength);
}
private HashMap<Haplotype,Integer> haplotypeToHaplotypeListIdxMap = null;
//Used to transfer data to JNI
//Since the haplotypes are the same for all calls to computeLikelihoods within a region, transfer the haplotypes only once to the JNI per region
/**
* {@inheritDoc}
*/
@Override
public void initialize( final List<Haplotype> haplotypes, final Map<String, List<GATKSAMRecord>> perSampleReadList,
final int readMaxLength, final int haplotypeMaxLength ) {
if(verify)
{
super.initialize(haplotypes, perSampleReadList, readMaxLength, haplotypeMaxLength);
jniPairHMM.initialize(haplotypes, perSampleReadList, readMaxLength, haplotypeMaxLength);
haplotypeToHaplotypeListIdxMap = jniPairHMM.getHaplotypeToHaplotypeListIdxMap();
}
}
/**
* {@inheritDoc}
*/
@Override
public void finalizeRegion()
{
if(!dumpSandboxOnly)
jniPairHMM.finalizeRegion();
}
/**
* {@inheritDoc}
*/
@Override
public void computeLikelihoods( final ReadLikelihoods.Matrix<Haplotype> likelihoods, final List<GATKSAMRecord> processedReads, final Map<GATKSAMRecord, byte[]> GCPArrayMap ) {
// (re)initialize the pairHMM only if necessary
final int readMaxLength = verify ? findMaxReadLength(processedReads) : 0;
final int haplotypeMaxLength = verify ? findMaxHaplotypeLength(likelihoods.alleles()) : 0;
if(verify)
{
if (!initialized || readMaxLength > maxReadLength || haplotypeMaxLength > maxHaplotypeLength)
{ initialize(readMaxLength, haplotypeMaxLength); }
if ( ! initialized )
throw new IllegalStateException("Must call initialize before calling jniComputeLikelihoods in debug/verify mode");
}
int readListSize = processedReads.size();
int numHaplotypes = likelihoods.alleleCount();
int numTestcases = readListSize*numHaplotypes;
if(debug0_1)
System.out.println("Java numReads "+readListSize+" numHaplotypes "+numHaplotypes);
int idx = 0;
for(final GATKSAMRecord read : processedReads)
{
final byte [] overallGCP = GCPArrayMap.get(read);
if(debug0_1)
System.out.println("Java read length "+read.getReadBases().length);
if(debug3)
{
for(int i=0;i<read.getReadBases().length;++i)
{
debugDump("reads_java.txt",String.format("%d\n",(int)read.getReadBases()[i]),true);
debugDump("reads_java.txt",String.format("%d\n",(int)read.getBaseQualities()[i]),true);
debugDump("reads_java.txt",String.format("%d\n",(int)read.getBaseInsertionQualities()[i]),true);
debugDump("reads_java.txt",String.format("%d\n",(int)read.getBaseDeletionQualities()[i]),true);
debugDump("reads_java.txt",String.format("%d\n",(int)overallGCP[i]),true);
}
}
++idx;
}
if(verify)
{
idx = 0;
for (final Haplotype h : likelihoods.alleles()) //order is important - access in same order always
{
byte[] haplotypeBases = h.getBases();
if(debug0_1)
System.out.println("Java haplotype length "+haplotypeBases.length);
if(debug3)
{
for(int i=0;i<haplotypeBases.length;++i)
debugDump("haplotype_bases_java.txt",String.format("%d\n",(int)haplotypeBases[i]),true);
}
++idx;
}
}
double[] likelihoodArray = null;
PerReadAlleleLikelihoodMap likelihoodMap = null;
if(verify)
{
jniPairHMM.computeLikelihoods(likelihoods, processedReads, GCPArrayMap);
likelihoodArray = jniPairHMM.getLikelihoodArray();
//to compare values
super.computeLikelihoods(likelihoods, processedReads, GCPArrayMap);
}
else
{
likelihoodMap = new PerReadAlleleLikelihoodMap();
likelihoodArray = new double[numTestcases];
for(int i=0;i<numTestcases;++i)
likelihoodArray[i] = -0.5;
}
if(verify || dumpSandboxOnly)
{
boolean toDump = dumpSandboxOnly ? true : false;
if(verify)
{
//re-order values in likelihoodArray
double[] tmpArray = new double[numHaplotypes];
idx = 0;
int idxInsideHaplotypeList = 0;
int readIdx = 0;
for(final GATKSAMRecord read : processedReads)
{
for(int j=0;j<numHaplotypes;++j)
tmpArray[j] = likelihoodArray[readIdx+j];
for (final Haplotype haplotype : likelihoods.alleles())//order is important - access in same order always
{
idxInsideHaplotypeList = haplotypeToHaplotypeListIdxMap.get(haplotype);
likelihoodArray[idx] = tmpArray[idxInsideHaplotypeList];
++idx;
}
readIdx += numHaplotypes;
}
//for floating point values, no exact equality
//check whether numbers are close in terms of abs_error or relative_error
//For very large values, relative_error is relevant
//For very small values, abs_error is relevant
for(int i=0;i<likelihoodArray.length;++i)
{
double abs_error = Math.abs(likelihoodArray[i] - mLikelihoodArray[i]);
double relative_error = 0;
if(mLikelihoodArray[i] == 0)
relative_error = 0;
else
relative_error = Math.abs(abs_error/mLikelihoodArray[i]);
if(abs_error > 1e-5 && relative_error > 1e-5)
{
toDump = true;
break;
}
}
}
//if numbers are not close, then dump out the data that produced the inconsistency
if(toDump)
{
idx = 0;
System.out.println("Dump : Java numReads "+readListSize+" numHaplotypes "+numHaplotypes);
boolean firstLine = true;
for(final GATKSAMRecord read : processedReads)
{
byte [] overallGCP = GCPArrayMap.get(read);
byte[] tmpByteArray = new byte[read.getReadBases().length];
for (final Haplotype haplotype : likelihoods.alleles()) //order is important - access in same order always
{
byte[] haplotypeBases = haplotype.getBases();
debugDump("debug_dump.txt",new String(haplotypeBases)+" ",true);
debugDump("debug_dump.txt",new String(read.getReadBases())+" ",true);
for(int k=0;k<read.getReadBases().length;++k)
tmpByteArray[k] = (byte)((int)((read.getBaseQualities())[k]) + 33);
debugDump("debug_dump.txt",new String(tmpByteArray)+" ",true);
for(int k=0;k<read.getReadBases().length;++k)
tmpByteArray[k] = (byte)((int)((read.getBaseInsertionQualities())[k]) + 33);
debugDump("debug_dump.txt",new String(tmpByteArray)+" ",true);
for(int k=0;k<read.getReadBases().length;++k)
tmpByteArray[k] = (byte)((int)((read.getBaseDeletionQualities())[k]) + 33);
debugDump("debug_dump.txt",new String(tmpByteArray)+" ",true);
for(int k=0;k<read.getReadBases().length;++k)
tmpByteArray[k] = (byte)((int)(overallGCP[k]) + 33);
debugDump("debug_dump.txt",new String(tmpByteArray),true);
if(firstLine)
{
debugDump("debug_dump.txt",String.format(" %d %d\n",readListSize, numHaplotypes), true);
firstLine = false;
}
else
debugDump("debug_dump.txt","\n",true);
if(verify)
debugDump("debug_results.txt",String.format("%e %e\n",mLikelihoodArray[idx],likelihoodArray[idx]),true);
else
if(dumpSandboxOnly)
likelihoods.set(likelihoods.alleleIndex(haplotype),likelihoods.readIndex(read), likelihoodArray[idx]);
++idx;
}
}
}
debugClose();
}
++numComputeLikelihoodCalls;
//if(numComputeLikelihoodCalls == 5)
//jniPairHMM.close();
//System.exit(0);
}
//Used to test parts of the compute kernel separately
private native void jniInitialize( final int readMaxLength, final int haplotypeMaxLength);
private native static void jniInitializeProbabilities( final double[][] transition, final byte[] insertionGOP,
final byte[] deletionGOP, final byte[] overallGCP);
private native double jniInitializePriorsAndUpdateCells( boolean doInitialization, final int paddedReadLength,
final int paddedHaplotypeLength, final byte[] readBases, final byte[] haplotypeBases, final byte[] readQuals,
final int hapStartIndex);
private native double jniSubComputeReadLikelihoodGivenHaplotypeLog10( final int readLength, final int haplotypeLength,
final byte[] readBases, final byte[] haplotypeBases, final byte[] readQuals, final byte[] insertionGOP,
final byte[] deletionGOP, final byte[] overallGCP, final int hapStartIndex);
/**
* {@inheritDoc}
*/
@Override
public double subComputeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases, final byte[] readBases,
final byte[] readQuals, final byte[] insertionGOP, final byte[] deletionGOP, final byte[] overallGCP,
final int hapStartIndex, final boolean recacheReadValues, final int nextHapStartIndex) {
//System.out.println("#### START STACK TRACE ####");
//for (StackTraceElement ste : Thread.currentThread().getStackTrace()) {
//System.out.println(ste);
//}
//System.out.println("#### END STACK TRACE ####");
//
if(debug1)
jniSubComputeReadLikelihoodGivenHaplotypeLog10(readBases.length, haplotypeBases.length,
readBases, haplotypeBases, readQuals,
insertionGOP, deletionGOP, overallGCP,
hapStartIndex);
boolean doInitialization = (previousHaplotypeBases == null || previousHaplotypeBases.length != haplotypeBases.length);
if (doInitialization) {
final double initialValue = INITIAL_CONDITION / haplotypeBases.length;
// set the initial value (free deletions in the beginning) for the first row in the deletion matrix
for( int j = 0; j < paddedHaplotypeLength; j++ ) {
deletionMatrix[0][j] = initialValue;
}
}
if ( ! constantsAreInitialized || recacheReadValues ) {
initializeProbabilities(transition, insertionGOP, deletionGOP, overallGCP);
if(debug3)
{
System.out.println("Java: initializeProbabilities lengths : "+insertionGOP.length+" padded "+paddedReadLength+" "+paddedHaplotypeLength);
for(int i=0;i<insertionGOP.length;++i)
for(int j=0;j<6;++j)
debugDump("transitions_java.txt",String.format("%e\n",transition[i+1][j]),true);
}
if(debug2)
jniInitializeProbabilities(transition, insertionGOP, deletionGOP, overallGCP);
// note that we initialized the constants
constantsAreInitialized = true;
}
if(debug3)
System.out.println("Java: initializePriors : lengths "+readBases.length+" "+haplotypeBases.length+" padded "+paddedReadLength+" "+paddedHaplotypeLength + " doNotUseTristateCorrection "+doNotUseTristateCorrection);
initializePriors(haplotypeBases, readBases, readQuals, hapStartIndex);
for (int i = 1; i < paddedReadLength; i++) {
// +1 here is because hapStartIndex is 0-based, but our matrices are 1 based
for (int j = hapStartIndex+1; j < paddedHaplotypeLength; j++) {
updateCell(i, j, prior[i][j], transition[i]);
}
}
// final probability is the log10 sum of the last element in the Match and Insertion state arrays
// this way we ignore all paths that ended in deletions! (huge)
// but we have to sum all the paths ending in the M and I matrices, because they're no longer extended.
final int endI = paddedReadLength - 1;
double finalSumProbabilities = 0.0;
for (int j = 1; j < paddedHaplotypeLength; j++) {
finalSumProbabilities += matchMatrix[endI][j] + insertionMatrix[endI][j];
}
if(debug2)
jniInitializePriorsAndUpdateCells(doInitialization, paddedReadLength, paddedHaplotypeLength,
readBases, haplotypeBases, readQuals,
hapStartIndex);
if(debug)
debugDump("return_values_java.txt",String.format("%e\n",Math.log10(finalSumProbabilities) - INITIAL_CONDITION_LOG10),true);
++numCalls;
//if(numCalls == 100)
//{
//debugClose();
//System.exit(0);
//}
return Math.log10(finalSumProbabilities) - INITIAL_CONDITION_LOG10;
}
/**
* Initializes the matrix that holds all the constants related to the editing
* distance between the read and the haplotype.
*
* @param haplotypeBases the bases of the haplotype
* @param readBases the bases of the read
* @param readQuals the base quality scores of the read
* @param startIndex where to start updating the distanceMatrix (in case this read is similar to the previous read)
*/
protected void initializePriors(final byte[] haplotypeBases, final byte[] readBases, final byte[] readQuals, final int startIndex) {
// initialize the pBaseReadLog10 matrix for all combinations of read x haplotype bases
// Abusing the fact that java initializes arrays with 0.0, so no need to fill in rows and columns below 2.
if(debug3)
System.out.println("hapStartIndex "+startIndex);
for (int i = 0; i < readBases.length; i++) {
final byte x = readBases[i];
final byte qual = readQuals[i];
for (int j = startIndex; j < haplotypeBases.length; j++) {
final byte y = haplotypeBases[j];
prior[i+1][j+1] = ( x == y || x == (byte) 'N' || y == (byte) 'N' ?
QualityUtils.qualToProb(qual) : (QualityUtils.qualToErrorProb(qual) / (doNotUseTristateCorrection ? 1.0 : TRISTATE_CORRECTION)) );
if(debug3)
debugDump("priors_java.txt",String.format("%e\n",prior[i+1][j+1]),true);
}
}
}
/**
* Initializes the matrix that holds all the constants related to quality scores.
*
* @param insertionGOP insertion quality scores of the read
* @param deletionGOP deletion quality scores of the read
* @param overallGCP overall gap continuation penalty
*/
@Requires({
"insertionGOP != null",
"deletionGOP != null",
"overallGCP != null"
})
@Ensures("constantsAreInitialized")
protected static void initializeProbabilities(final double[][] transition, final byte[] insertionGOP, final byte[] deletionGOP, final byte[] overallGCP) {
PairHMMModel.qualToTransProbs(transition,insertionGOP,deletionGOP,overallGCP);
}
/**
* Updates a cell in the HMM matrix
*
* The read and haplotype indices are offset by one because the state arrays have an extra column to hold the
* initial conditions
* @param indI row index in the matrices to update
* @param indJ column index in the matrices to update
* @param prior the likelihood editing distance matrix for the read x haplotype
* @param transition an array with the six transition relevant to this location
*/
protected void updateCell( final int indI, final int indJ, final double prior, final double[] transition) {
matchMatrix[indI][indJ] = prior * ( matchMatrix[indI - 1][indJ - 1] * transition[matchToMatch] +
insertionMatrix[indI - 1][indJ - 1] * transition[indelToMatch] +
deletionMatrix[indI - 1][indJ - 1] * transition[indelToMatch] );
insertionMatrix[indI][indJ] = matchMatrix[indI - 1][indJ] * transition[matchToInsertion] + insertionMatrix[indI - 1][indJ] * transition[insertionToInsertion];
deletionMatrix[indI][indJ] = matchMatrix[indI][indJ - 1] * transition[matchToDeletion] + deletionMatrix[indI][indJ - 1] * transition[deletionToDeletion];
if(debug3)
{
debugDump("matrices_java.txt",String.format("%e\n",matchMatrix[indI][indJ]),true);
debugDump("matrices_java.txt",String.format("%e\n",insertionMatrix[indI][indJ]),true);
debugDump("matrices_java.txt",String.format("%e\n",deletionMatrix[indI][indJ]),true);
}
}
protected void debugDump( String filename, String s, boolean toAppend ) {
try {
File file = new File(filename);
if (!file.exists())
file.createNewFile();
BufferedWriter currWriter = filenameToWriter.get(filename);
if(currWriter == null)
{
FileWriter fw = new FileWriter(file, toAppend);
currWriter = new BufferedWriter(fw);
filenameToWriter.put(filename, currWriter);
}
currWriter.write(s);
}
catch(IOException e)
{
e.printStackTrace();
}
}
protected void debugClose() {
for(Map.Entry<String, BufferedWriter> currEntry : filenameToWriter.entrySet()) {
BufferedWriter currWriter = currEntry.getValue();
try
{
currWriter.flush();
currWriter.close();
}
catch(IOException e)
{
e.printStackTrace();
}
}
filenameToWriter.clear();
}
}