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mostly synchronizing with the main branch. Based on anecdotal evidence (too few examples in the data), realignment (shifting indel left across a repeat) works correctly on non-homonucleotide repeats 

git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@928 348d0f76-0448-11de-a6fe-93d51630548a
This commit is contained in:
asivache 2009-06-07 16:39:16 +00:00
parent c6634e3121
commit 9eb38c0222
1 changed files with 56 additions and 48 deletions
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104
java/src/org/broadinstitute/sting/playground/gatk/walkers/indels/IntervalCleanerWalker.java
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@ -1,4 +1,3 @@
package org.broadinstitute.sting.playground.gatk.walkers.indels;
import org.broadinstitute.sting.utils.*;
@ -10,7 +9,6 @@ import org.broadinstitute.sting.utils.cmdLine.Argument;
import org.broadinstitute.sting.playground.indels.*;
import net.sf.samtools.*;
import java.util.*;
import java.io.File;
import java.io.FileNotFoundException;
@ -45,7 +43,7 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
private TreeSet<ComparableSAMRecord> readsToWrite;
public void initialize() {
if ( LOD_THRESHOLD < 0.0 )
throw new RuntimeException("LOD threshold cannot be a negative number");
@ -59,7 +57,7 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
try {
indelOutput = new FileWriter(new File(OUT_INDELS));
} catch (Exception e) {
logger.warn("Failed to create output file "+ OUT_INDELS+". Indel output will be suppressed");
logger.warn("Failed to create output file "+ OUT_INDELS+". Indel output will be suppressed");
err.println(e.getMessage());
indelOutput = null;
}
@ -68,7 +66,7 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
try {
statsOutput = new FileWriter(new File(OUT_STATS));
} catch (Exception e) {
logger.warn("Failed to create output file "+ OUT_STATS+". Cleaning stats output will be suppressed");
logger.warn("Failed to create output file "+ OUT_STATS+". Cleaning stats output will be suppressed");
err.println(e.getMessage());
statsOutput = null;
}
@ -83,13 +81,13 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
// What do we do with the reads that are not part of our intervals?
public void nonIntervalReadAction(SAMRecord read) {
try {
writer.addAlignment(read);
} catch (Exception e ) {
logger.error("Failed to write read "+read.getReadName()+" aligned at "+read.getReferenceName() +":"+read.getAlignmentStart());
e.printStackTrace(out);
throw new StingException(e.getMessage());
}
try {
writer.addAlignment(read);
} catch (Exception e ) {
logger.error("Failed to write read "+read.getReadName()+" aligned at "+read.getReferenceName() +":"+read.getAlignmentStart());
e.printStackTrace(out);
throw new StingException(e.getMessage());
}
}
public Integer map(RefMetaDataTracker tracker, String ref, LocusContext context) {
@ -133,14 +131,14 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
try {
indelOutput.close();
} catch (Exception e) {
logger.error("Failed to close "+OUT_INDELS+" gracefully. Data may be corrupt.");
logger.error("Failed to close "+OUT_INDELS+" gracefully. Data may be corrupt.");
}
}
if ( OUT_STATS != null ) {
try {
statsOutput.close();
} catch (Exception e) {
logger.error("Failed to close "+OUT_STATS+" gracefully. Data may be corrupt.");
logger.error("Failed to close "+OUT_STATS+" gracefully. Data may be corrupt.");
}
}
}
@ -540,8 +538,8 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
* @return a cigar, in which indel is guaranteed to be placed at the leftmost possible position across a repeat (if any)
*/
private Cigar indelRealignment(Cigar cigar, String refSeq, String readSeq, int refIndex, boolean readIsConsensusSequence) {
if ( cigar.numCigarElements() < 2 ) return cigar; // no indels, nothing to do
if ( cigar.numCigarElements() < 2 ) return cigar; // no indels, nothing to do
CigarElement ce1 = cigar.getCigarElement(0);
CigarElement ce2 = cigar.getCigarElement(1);
@ -558,19 +556,20 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
int start = ce1.getLength() + (readIsConsensusSequence ? refIndex : 0);
indelString = readSeq.substring(start, start+ce2.getLength()).toUpperCase(); // get the inserted bases
}
// now we have to check all WHOLE periods of the indel sequence:
// for instance, if
// REF: AGCTATATATAGCC
// READ: GCTAT***TAGCC
// READ: GCTAT***TAGCC
// the deleted sequence ATA does have period of 2, but deletion obviously can not be
// shifted left by 2 bases (length 3 does not contain whole number of periods of 2);
// however if 4 bases are deleted:
// REF: AGCTATATATAGCC
// READ: GCTA****TAGCC
// READ: GCTA****TAGCC
// the length 4 is a multiple of the period of 2, and indeed deletion site can be moved left by 2 bases!
// We will always have to check the length of the indel sequence itself (trivial period), unless the smallest
// period is 1 (which means that indel sequence is a homo-nucleotide sequence so we can just step left
// one base at a time as long as we get a match)
// Also, we will always have to check the length of the indel sequence itself (trivial period). If the smallest
// period is 1 (which means that indel sequence is a homo-nucleotide sequence), we obviously do not have to check
// any other periods.
// NOTE: we treat both insertions and deletions in the same way below: we always check if the indel sequence
// repeats itsels on the REF (never on the read!), even for insertions: if we see TA inserted and REF has, e.g., CATATA prior to the insertion
@ -578,45 +577,54 @@ public class IntervalCleanerWalker extends LocusWindowWalker<Integer, Integer>
while ( period < indel_length ) { // we will always get at least trivial period = indelStringLength
period = BaseUtils.sequencePeriod(indelString, period+1);
if ( indel_length % period != 0 ) continue; // period is not a multiple of indel sequence length
period = BaseUtils.sequencePeriod(indelString, period+1);
int newIndex = indexOnRef;
while ( newIndex >= period ) { // let's see if there is a repeat, i.e. if we could also say that same bases at lower position are deleted
// lets check if bases [newIndex-period,newIndex) immediately preceding the indel on the ref
// are the same as the currently checked period of the inserted sequence:
boolean match = true;
for ( int testRefPos = newIndex - period, indelPos = 0 ; testRefPos < newIndex; testRefPos++, indelPos++) {
if ( Character.toUpperCase(refSeq.charAt(testRefPos)) != indelString.charAt(indelPos) ) {
match = false;
break;
}
}
if ( match )
newIndex -= period; // yes, they are the same, we can move indel farther left by at least period bases, go check if we can do more...
else break; // oops, no match, can not push indel farther left
}
if ( indel_length % period != 0 ) continue; // period is not a multiple of indel sequence length
int newIndex = indexOnRef;
while ( newIndex >= period ) { // let's see if there is a repeat, i.e. if we could also say that same bases at lower position are deleted
// lets check if bases [newIndex-period,newIndex) immediately preceding the indel on the ref
// are the same as the currently checked period of the inserted sequence:
boolean match = true;
for ( int testRefPos = newIndex - period, indelPos = 0 ; testRefPos < newIndex; testRefPos++, indelPos++) {
if ( Character.toUpperCase(refSeq.charAt(testRefPos)) != indelString.charAt(indelPos) ) {
match = false;
break;
}
}
if ( match )
newIndex -= period; // yes, they are the same, we can move indel farther left by at least period bases, go check if we can do more...
else break; // oops, no match, can not push indel farther left
}
final int newDifference = indexOnRef - newIndex;
if ( newDifference > difference ) difference = newDifference; // deletion should be moved 'difference' bases left
final int newDifference = indexOnRef - newIndex;
if ( newDifference > difference ) difference = newDifference; // deletion should be moved 'difference' bases left
if ( period == 1 ) break; // we do not have to check all periods of homonucleotide sequences, we already
// got maximum possible shift after checking period=1 above.
if ( period == 1 ) break; // we do not have to check all periods of homonucleotide sequences, we already
// got maximum possible shift after checking period=1 above.
}
// if ( ce2.getLength() >= 2 )
// System.out.println("-----------------------------------\n FROM:\n"+AlignmentUtils.alignmentToString(cigar,readSeq,refSeq,refIndex, (readIsConsensusSequence?refIndex:0)));
if ( difference > 0 ) {
Cigar newCigar = new Cigar();
newCigar.add(new CigarElement(ce1.getLength()-difference, CigarOperator.M));
newCigar.add(ce2);
newCigar.add(new CigarElement(cigar.getCigarElement(2).getLength()+difference, CigarOperator.M));
// System.out.println(" FROM:\n"+AlignmentUtils.alignmentToString(cigar,readSeq,refSeq,refIndex));
// if ( ce2.getLength() >=2 )
// System.out.println(" REALIGNED TO:\n"+AlignmentUtils.alignmentToString(newCigar,readSeq,refSeq,refIndex,(readIsConsensusSequence?refIndex:0))+"\n");
logger.debug("Realigning indel: " + cigarToString(cigar) + " to " + cigarToString(newCigar));
cigar = newCigar;
}
return cigar;
}