Merge branch 'master' of ssh://chartl@ni.broadinstitute.org/humgen/gsa-scr1/gsa-engineering/git/unstable

public/java/src/org/broadinstitute/sting/gatk/datasources/reads/BlockInputStream.java

@@ -443,7 +443,16 @@ public class BlockInputStream extends SeekableStream implements BAMInputStream {
 //            }
 //        }
 
-        return eof() ? -1 : length-remaining;
+        // If any data was copied into the buffer, return the amount of data copied.
+        if(remaining < length)
+            return length - remaining;
+
+        // Otherwise, if at eof(), return -1.
+        else if(eof())
+            return -1;
+
+        // Otherwise, we must've hit a bug in the system.
+        throw new ReviewedStingException("BUG: read returned no data, but eof() reports false.");
     }
 
     public void close() {

public/java/src/org/broadinstitute/sting/gatk/iterators/LocusIteratorByState.java

@@ -193,6 +193,9 @@ public class LocusIteratorByState extends LocusIterator {
                     // we reenter in order to re-check cigarElementCounter against curElement's length
                     return stepForwardOnGenome();
                 } else {
+                    if (curElement != null && curElement.getOperator() == CigarOperator.D)
+                        throw new UserException.MalformedBAM(read, "read ends with deletion. Cigar: " + read.getCigarString());
+                        
                     // Reads that contain indels model the genomeOffset as the following base in the reference.  Because
                     // we fall into this else block only when indels end the read, increment genomeOffset  such that the
                     // current offset of this read is the next ref base after the end of the indel.  This position will
@@ -228,7 +231,7 @@ public class LocusIteratorByState extends LocusIterator {
                         // we see insertions only once, when we step right onto them; the position on the read is scrolled
                         // past the insertion right after that
                         if (eventDelayedFlag > 1)
-                            throw new UserException.MalformedBAM(read, "Adjacent I/D events in read " + read.getReadName());
+                            throw new UserException.MalformedBAM(read, String.format("Adjacent I/D events in read %s -- cigar: %s", read.getReadName(), read.getCigarString()));
                         insertedBases = Arrays.copyOfRange(read.getReadBases(), readOffset + 1, readOffset + 1 + curElement.getLength());
                         eventLength = curElement.getLength();
                         eventStart = readOffset;
@@ -247,7 +250,7 @@ public class LocusIteratorByState extends LocusIterator {
                             // generate an extended event only if we just stepped into the deletion (i.e. don't
                             // generate the event at every deleted position on the ref, that's what cigarElementCounter==1 is for!)
                             if (eventDelayedFlag > 1)
-                                throw new UserException.MalformedBAM(read, "Adjacent I/D events in read " + read.getReadName());
+                                throw new UserException.MalformedBAM(read, String.format("Adjacent I/D events in read %s -- cigar: %s", read.getReadName(), read.getCigarString()));
                             eventLength = curElement.getLength();
                             eventDelayedFlag = 2; // deletion on the ref causes an immediate return, so we have to delay by 1 only
                             eventStart = readOffset;

public/java/src/org/broadinstitute/sting/gatk/walkers/annotator/TransmissionDisequilibriumTest.java

@@ -7,6 +7,7 @@ import org.broadinstitute.sting.gatk.samples.Sample;
 import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.AnnotatorCompatibleWalker;
 import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.ExperimentalAnnotation;
 import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.InfoFieldAnnotation;
+import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.RodRequiringAnnotation;
 import org.broadinstitute.sting.utils.MathUtils;
 import org.broadinstitute.sting.utils.codecs.vcf.VCFHeaderLineType;
 import org.broadinstitute.sting.utils.codecs.vcf.VCFInfoHeaderLine;
@@ -17,16 +18,13 @@ import java.util.*;
 
 /**
  * Created by IntelliJ IDEA.
- * User: rpoplin, lfran
+ * User: rpoplin, lfran, ebanks
  * Date: 11/14/11
  */
 
-public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implements ExperimentalAnnotation {
+public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implements ExperimentalAnnotation, RodRequiringAnnotation {
 
     private Set<Sample> trios = null;
-    private final static int REF = 0;
-    private final static int HET = 1;
-    private final static int HOM = 2;
     private final static int MIN_NUM_VALID_TRIOS = 5; // don't calculate this population-level statistic if there are less than X trios with full genotype likelihood information
 
     public Map<String, Object> annotate(RefMetaDataTracker tracker, AnnotatorCompatibleWalker walker, ReferenceContext ref, Map<String, AlignmentContext> stratifiedContexts, VariantContext vc) {
@@ -38,10 +36,10 @@ public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implemen
             }
         }
 
-        final Map<String,Object> toRet = new HashMap<String,Object>(1);
+        final Map<String, Object> toRet = new HashMap<String, Object>(1);
         final HashSet<Sample> triosToTest = new HashSet<Sample>();
 
-        for( final Sample child : trios) {
+        for( final Sample child : trios ) {
             final boolean hasAppropriateGenotypes = vc.hasGenotype(child.getID()) && vc.getGenotype(child.getID()).hasLikelihoods() &&
                     vc.hasGenotype(child.getPaternalID()) && vc.getGenotype(child.getPaternalID()).hasLikelihoods() &&
                     vc.hasGenotype(child.getMaternalID()) && vc.getGenotype(child.getMaternalID()).hasLikelihoods();
@@ -65,28 +63,54 @@ public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implemen
     // Following derivation in http://en.wikipedia.org/wiki/Transmission_disequilibrium_test#A_modified_version_of_the_TDT
     private double calculateTDT( final VariantContext vc, final Set<Sample> triosToTest ) {
 
-        final double nABGivenABandBB = calculateNChildren(vc, triosToTest, HET, HET, HOM) + calculateNChildren(vc, triosToTest, HET, HOM, HET);
+        double nABGivenABandBB = 0.0;
-        final double nBBGivenABandBB = calculateNChildren(vc, triosToTest, HOM, HET, HOM) + calculateNChildren(vc, triosToTest, HOM, HOM, HET);
+        double nBBGivenABandBB = 0.0;
-        final double nAAGivenABandAB = calculateNChildren(vc, triosToTest, REF, HET, HET);
+        double nAAGivenABandAB = 0.0;
-        final double nBBGivenABandAB = calculateNChildren(vc, triosToTest, HOM, HET, HET);
+        double nBBGivenABandAB = 0.0;
-        final double nAAGivenAAandAB = calculateNChildren(vc, triosToTest, REF, REF, HET) + calculateNChildren(vc, triosToTest, REF, HET, REF);
+        double nAAGivenAAandAB = 0.0;
-        final double nABGivenAAandAB = calculateNChildren(vc, triosToTest, HET, REF, HET) + calculateNChildren(vc, triosToTest, HET, HET, REF);
+        double nABGivenAAandAB = 0.0;
+
+        // for each pair of alleles, add the likelihoods
+        int numAlleles = vc.getNAlleles();
+        for ( int allele1 = 0; allele1 < numAlleles; allele1++ ) {
+            for ( int allele2 = allele1 + 1; allele2 < numAlleles; allele2++ ) {
+
+                // TODO -- cache these for better performance
+                final int HOM1index = determineHomIndex(allele1, numAlleles);
+                final int HETindex = HOM1index + (allele2 - allele1);
+                final int HOM2index = determineHomIndex(allele2, numAlleles);
+
+                nABGivenABandBB += calculateNChildren(vc, triosToTest, HETindex, HETindex, HOM2index) + calculateNChildren(vc, triosToTest, HETindex, HOM2index, HETindex);
+                nBBGivenABandBB += calculateNChildren(vc, triosToTest, HOM2index, HETindex, HOM2index) + calculateNChildren(vc, triosToTest, HOM2index, HOM2index, HETindex);
+                nAAGivenABandAB += calculateNChildren(vc, triosToTest, HOM1index, HETindex, HETindex);
+                nBBGivenABandAB += calculateNChildren(vc, triosToTest, HOM2index, HETindex, HETindex);
+                nAAGivenAAandAB += calculateNChildren(vc, triosToTest, HOM1index, HOM1index, HETindex) + calculateNChildren(vc, triosToTest, HOM1index, HETindex, HOM1index);
+                nABGivenAAandAB += calculateNChildren(vc, triosToTest, HETindex, HOM1index, HETindex) + calculateNChildren(vc, triosToTest, HETindex, HETindex, HOM1index);
+            }
+        }
 
         final double numer = (nABGivenABandBB - nBBGivenABandBB) + 2.0 * (nAAGivenABandAB - nBBGivenABandAB) + (nAAGivenAAandAB - nABGivenAAandAB);
         final double denom = (nABGivenABandBB + nBBGivenABandBB) + 4.0 * (nAAGivenABandAB + nBBGivenABandAB) + (nAAGivenAAandAB + nABGivenAAandAB);
         return (numer * numer) / denom;
     }
 
-    private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int parent1Idx, final int parent2Idx ) {
+    private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int momIdx, final int dadIdx ) {
         final double likelihoodVector[] = new double[triosToTest.size()];
         int iii = 0;
         for( final Sample child : triosToTest ) {
             final double[] momGL = vc.getGenotype(child.getMaternalID()).getLikelihoods().getAsVector();
             final double[] dadGL = vc.getGenotype(child.getPaternalID()).getLikelihoods().getAsVector();
             final double[] childGL = vc.getGenotype(child.getID()).getLikelihoods().getAsVector();
-            likelihoodVector[iii++] = momGL[parent1Idx] + dadGL[parent2Idx] + childGL[childIdx];
+            likelihoodVector[iii++] = momGL[momIdx] + dadGL[dadIdx] + childGL[childIdx];
         }
 
         return MathUtils.sumLog10(likelihoodVector);
     }
+    
+    private static int determineHomIndex(final int alleleIndex, int numAlleles) {
+        int result = 0;
+        for ( int i = 0; i < alleleIndex; i++ )
+            result += numAlleles--;
+        return result;
+    }
 }

public/java/src/org/broadinstitute/sting/gatk/walkers/recalibration/CountCovariatesWalker.java

@@ -377,7 +377,6 @@ public class CountCovariatesWalker extends LocusWalker<CountCovariatesWalker.Cou
                             RecalDataManager.computeCovariates( gatkRead, requestedCovariates ));
                 }
 
-
                 // Skip this position if base quality is zero
                 if( gatkRead.getBaseQualities()[offset] > 0 ) {
 

public/java/src/org/broadinstitute/sting/utils/pileup/PileupElement.java

@@ -4,6 +4,7 @@ import com.google.java.contract.Ensures;
 import com.google.java.contract.Requires;
 import org.broadinstitute.sting.utils.BaseUtils;
 import org.broadinstitute.sting.utils.exceptions.ReviewedStingException;
+import org.broadinstitute.sting.utils.exceptions.UserException;
 import org.broadinstitute.sting.utils.sam.GATKSAMRecord;
 
 /**
@@ -146,9 +147,12 @@ public class PileupElement implements Comparable<PileupElement> {
     public int getRepresentativeCount() {
         int representativeCount = 1;
 
-        if (read.isReducedRead() && !isInsertionAtBeginningOfRead())
+        if (read.isReducedRead() && !isInsertionAtBeginningOfRead())     {
-            representativeCount = (isDeletion()) ? Math.round((read.getReducedCount(offset) + read.getReducedCount(offset + 1)) / 2) : read.getReducedCount(offset);
+            if (isDeletion() && (offset + 1 >= read.getReadLength()) )  // deletion in the end of the read
+                throw new UserException.MalformedBAM(read, String.format("Adjacent I/D events in read %s -- cigar: %s", read.getReadName(), read.getCigarString()));
 
+            representativeCount = (isDeletion()) ? Math.round((read.getReducedCount(offset) + read.getReducedCount(offset + 1)) / 2) : read.getReducedCount(offset);
+        }
         return representativeCount;
     }