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Complex SV intervals support #8521

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merged 3 commits into from
Jul 11, 2024
Merged

Complex SV intervals support #8521

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e906b51
Improve ctx handling; remove end2/chr2 from cpx
mwalker174 Aug 25, 2023
5b60b2e
Do not assume sorted complex intervals
mwalker174 Jul 9, 2024
8c04685
Undo COMPLEX_POINT_SUBTYPES
mwalker174 Jul 11, 2024
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9 changes: 9 additions & 0 deletions src/main/java/org/broadinstitute/hellbender/tools/spark/sv/utils/GATKSVVCFConstants.java
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Original file line number Diff line number Diff line change
Expand Up @@ -2,8 +2,10 @@

import com.google.common.collect.HashBiMap;
import htsjdk.variant.variantcontext.Allele;
import org.aeonbits.owner.util.Collections;

import java.util.Map;
import java.util.Set;

import static java.util.Map.entry;

Expand Down Expand Up @@ -121,6 +123,13 @@ public enum ComplexVariantSubtype {
entry("CTX_INV", ComplexVariantSubtype.CTX_INV)
));

// complex subtypes expected to have POS=END
public static final Set<ComplexVariantSubtype> COMPLEX_POINT_SUBTYPES =
Collections.set(
GATKSVVCFConstants.ComplexVariantSubtype.dDUP,
GATKSVVCFConstants.ComplexVariantSubtype.dDUP_iDEL
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dDUP_iDEL events don't have POS = END because there is a deletion at the sink

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I couldn't actually find where this constant gets used though?

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Whoops. I was considering this but didn't end up using it

);

// not defined in output vcf header but used in internal id that is currently output in the ID column
public static final String INTERVAL_VARIANT_ID_FIELD_SEPARATOR = "_";
public static final String DUP_TAN_CONTRACTION_INTERNAL_ID_START_STRING = "DEL-DUPLICATION-TANDEM-CONTRACTION";
Expand Down
74 changes: 69 additions & 5 deletions src/main/java/org/broadinstitute/hellbender/tools/sv/SVCallRecord.java
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Expand Up @@ -10,6 +10,7 @@
import htsjdk.variant.vcf.VCFConstants;
import org.apache.commons.lang3.tuple.Pair;
import org.broadinstitute.hellbender.tools.spark.sv.utils.GATKSVVCFConstants;
import org.broadinstitute.hellbender.tools.walkers.sv.SVSegment;
import org.broadinstitute.hellbender.utils.IntervalUtils;
import org.broadinstitute.hellbender.utils.SimpleInterval;
import org.broadinstitute.hellbender.utils.Utils;
Expand All @@ -34,7 +35,8 @@ public class SVCallRecord implements SVLocatable {
GATKSVVCFConstants.END2_ATTRIBUTE,
GATKSVVCFConstants.STRANDS_ATTRIBUTE,
GATKSVVCFConstants.SVTYPE,
GATKSVVCFConstants.CPX_TYPE
GATKSVVCFConstants.CPX_TYPE,
GATKSVVCFConstants.CPX_INTERVALS
);

private final String id;
Expand All @@ -57,6 +59,7 @@ public class SVCallRecord implements SVLocatable {

// CPX related fields
private final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype;
private final List<ComplexEventInterval> cpxIntervals;

public SVCallRecord(final String id,
final String contigA,
Expand All @@ -67,6 +70,7 @@ public SVCallRecord(final String id,
final Boolean strandB,
final GATKSVVCFConstants.StructuralVariantAnnotationType type,
final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype,
final List<ComplexEventInterval> cpxIntervals,
final Integer length,
final List<String> algorithms,
final List<Allele> alleles,
Expand All @@ -75,7 +79,7 @@ public SVCallRecord(final String id,
final Set<String> filters,
final Double log10PError,
final SAMSequenceDictionary dictionary) {
this(id, contigA, positionA, strandA, contigB, positionB, strandB, type, cpxSubtype, length, algorithms, alleles, genotypes, attributes, filters, log10PError);
this(id, contigA, positionA, strandA, contigB, positionB, strandB, type, cpxSubtype, cpxIntervals, length, algorithms, alleles, genotypes, attributes, filters, log10PError);
validateCoordinates(dictionary);
}

Expand All @@ -88,6 +92,7 @@ protected SVCallRecord(final String id,
final Boolean strandB,
final GATKSVVCFConstants.StructuralVariantAnnotationType type,
final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype,
final List<ComplexEventInterval> cpxIntervals,
final Integer length,
final List<String> algorithms,
final List<Allele> alleles,
Expand All @@ -100,13 +105,15 @@ protected SVCallRecord(final String id,
Utils.nonNull(genotypes);
Utils.nonNull(attributes);
Utils.nonNull(filters);
Utils.nonNull(cpxIntervals);
this.id = Utils.nonNull(id);
this.contigA = contigA;
this.positionA = positionA;
this.contigB = contigB;
this.positionB = positionB;
this.type = Utils.nonNull(type);
this.cpxSubtype = cpxSubtype;
this.cpxIntervals = canonicalizeComplexEventList(cpxIntervals);
this.algorithms = Collections.unmodifiableList(algorithms);
this.alleles = Collections.unmodifiableList(alleles);
this.altAlleles = alleles.stream().filter(allele -> !allele.isNoCall() && !allele.isReference()).collect(Collectors.toList());
Expand Down Expand Up @@ -135,11 +142,26 @@ private void validateCoordinates(final SAMSequenceDictionary dictionary) {
// CPX types may have position B precede A, such as dispersed duplications where A is the insertion point and
// B references the source sequence.
if (type != GATKSVVCFConstants.StructuralVariantAnnotationType.CPX) {
Utils.validateArg(IntervalUtils.compareLocatables(getPositionAInterval(), getPositionBInterval(), dictionary) <= 0,
"End coordinate cannot precede start");
if (IntervalUtils.compareLocatables(getPositionAInterval(), getPositionBInterval(), dictionary) > 0) {
throw new IllegalArgumentException("End precedes start in variant " + id);
}
}
for (final ComplexEventInterval interval : cpxIntervals) {
Utils.nonNull(interval);
validatePosition(interval.getContig(), interval.getStart(), dictionary);
validatePosition(interval.getContig(), interval.getEnd(), dictionary);
}
}

/**
* Sorts complex intervals list so that they can be efficiently compared across records.
* @param intervals complex intervals
* @return canonicalized list
*/
private static List<ComplexEventInterval> canonicalizeComplexEventList(final List<ComplexEventInterval> intervals) {
return intervals.stream().sorted(Comparator.comparing(ComplexEventInterval::encode)).collect(Collectors.toList());
}

private static void validatePosition(final String contig, final int position, final SAMSequenceDictionary dictionary) {
final SAMSequenceRecord seq = dictionary.getSequence(contig);
Utils.validateArg(seq != null, "Contig " + contig + " not found in dictionary");
Expand All @@ -148,7 +170,7 @@ private static void validatePosition(final String contig, final int position, fi

private static Map<String, Object> validateAttributes(final Map<String, Object> attributes) {
for (final String key : INVALID_ATTRIBUTES) {
Utils.validateArg(!attributes.containsKey(key), "Attempted to create record with invalid key: " + key);
Utils.validateArg(!attributes.containsKey(key), "Attempted to create record with reserved key: " + key);
}
return attributes;
}
Expand Down Expand Up @@ -180,6 +202,7 @@ private static Integer inferLength(final GATKSVVCFConstants.StructuralVariantAnn
|| type == GATKSVVCFConstants.StructuralVariantAnnotationType.CTX) && inputLength != null) {
throw new IllegalArgumentException("Input length should be null for type " + type.name() + " but found " + inputLength);
}
// TODO complex subtypes should be checked and handled properly, but for now we just pass through SVLEN
return inputLength;
}
}
Expand Down Expand Up @@ -384,4 +407,45 @@ public Double getLog10PError() {
return log10PError;
}

public List<ComplexEventInterval> getComplexEventIntervals() {
return cpxIntervals;
}

public static final class ComplexEventInterval extends SVSegment {

public ComplexEventInterval(final GATKSVVCFConstants.StructuralVariantAnnotationType intervalType,
final SimpleInterval interval) {
super(intervalType, interval);
}

public static ComplexEventInterval decode(final String str, final SAMSequenceDictionary dictionary) {
Utils.nonNull(str);
final String[] tokens = str.split("_", 2);
if (tokens.length < 2) {
throw new IllegalArgumentException("Expected complex interval with format \"SVTYPE_chr:pos-end\" but found \"" + str + "\"");
}
final SimpleInterval interval = new SimpleInterval(tokens[1]);
if (!IntervalUtils.intervalIsOnDictionaryContig(interval, dictionary)) {
throw new IllegalArgumentException("Invalid CPX interval: " + interval);
}
return new ComplexEventInterval(GATKSVVCFConstants.StructuralVariantAnnotationType.valueOf(tokens[0]), interval);
}

public String encode() {
return getIntervalSVType().name() + "_" + getInterval().toString();
}

@Override
public boolean equals(Object o) {
if (this == o) return true;
if (o == null || getClass() != o.getClass()) return false;
ComplexEventInterval that = (ComplexEventInterval) o;
return getIntervalSVType() == that.getIntervalSVType() && Objects.equals(getInterval(), that.getInterval());
}

@Override
public int hashCode() {
return Objects.hash(getIntervalSVType(), getInterval());
}
}
}
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