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Add SVStratify and GroupedSVCluster tools #8990

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Nov 18, 2024
Merged

Add SVStratify and GroupedSVCluster tools #8990

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d744b2b
Require both overlap and breakend proximity for depth-only SV clustering
mwalker174 Aug 23, 2024
473d484
Add vcf splitting as an option
mwalker174 Oct 2, 2024
8751795
Reviewer comments
mwalker174 Oct 24, 2024
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17 changes: 17 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 @@ -13,6 +13,7 @@ public final class GATKSVVCFConstants {
// VCF standard keys reserved for sv
public static final String SVTYPE = "SVTYPE";
public static final String SVLEN = "SVLEN";
public static final String EVIDENCE = "EVIDENCE";
public static final String IMPRECISE = "IMPRECISE";
public static final String CIPOS = "CIPOS";
public static final String CIEND = "CIEND";
Expand All @@ -31,6 +32,14 @@ public final class GATKSVVCFConstants {
public static final Allele DEL_ALLELE = Allele.create("<DEL>", false);
public static final Allele DUP_ALLELE = Allele.create("<DUP>", false);

// Evidence types
public enum EvidenceTypes {
BAF,
PE,
RD,
SR
}

// GATK-SV specific header lines
// TODO: 10/3/17 the following comment is a goal we are trying to achieve
// applicable to all records all the time
Expand Down Expand Up @@ -136,8 +145,13 @@ public enum ComplexVariantSubtype {
public static final String BND_DELETION_STRANDS = "+-";
public static final String BND_DUPLICATION_STRANDS = "-+";

// SR support
public static final String BOTHSIDES_SUPPORT_ATTRIBUTE = "BOTHSIDES_SUPPORT";
public static final String HIGH_SR_BACKGROUND_ATTRIBUTE = "HIGH_SR_BACKGROUND";

// format block
public static final String COPY_NUMBER_FORMAT = "CN";
public static final String DEPTH_GENOTYPE_COPY_NUMBER_FORMAT = "RD_CN";
public static final String EXPECTED_COPY_NUMBER_FORMAT = "ECN";
public static final String COPY_NUMBER_QUALITY_FORMAT = "CNQ";

Expand Down Expand Up @@ -175,6 +189,9 @@ public enum ComplexVariantSubtype {
public static final String TRUTH_ALLELE_NUMBER_INFO = "TRUTH_AN";
public static final String TRUTH_ALLELE_FREQUENCY_INFO = "TRUTH_AF";

// stratification
public static final String STRATUM_INFO_KEY = "STRAT";

// functional annotations
public static final String LOF = "PREDICTED_LOF";
public static final String INT_EXON_DUP = "PREDICTED_INTRAGENIC_EXON_DUP";
Expand Down
16 changes: 14 additions & 2 deletions src/main/java/org/broadinstitute/hellbender/tools/sv/SVCallRecord.java
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Original file line number Diff line number Diff line change
Expand Up @@ -21,6 +21,7 @@
import java.util.stream.Stream;

import static org.broadinstitute.hellbender.tools.spark.sv.utils.GATKSVVCFConstants.COPY_NUMBER_FORMAT;
import static org.broadinstitute.hellbender.tools.spark.sv.utils.GATKSVVCFConstants.DEPTH_GENOTYPE_COPY_NUMBER_FORMAT;

public class SVCallRecord implements SVLocatable {

Expand All @@ -31,6 +32,7 @@ public class SVCallRecord implements SVLocatable {
VCFConstants.END_KEY,
GATKSVVCFConstants.ALGORITHMS_ATTRIBUTE,
GATKSVVCFConstants.SVLEN,
GATKSVVCFConstants.EVIDENCE,
GATKSVVCFConstants.CONTIG2_ATTRIBUTE,
GATKSVVCFConstants.END2_ATTRIBUTE,
GATKSVVCFConstants.STRANDS_ATTRIBUTE,
Expand All @@ -48,6 +50,7 @@ public class SVCallRecord implements SVLocatable {
private final Boolean strandB;
private final GATKSVVCFConstants.StructuralVariantAnnotationType type;
private final Integer length;
private final List<GATKSVVCFConstants.EvidenceTypes> evidence;
private final List<String> algorithms;
private final List<Allele> alleles;
private final Allele refAllele;
Expand All @@ -72,14 +75,15 @@ public SVCallRecord(final String id,
final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype,
final List<ComplexEventInterval> cpxIntervals,
final Integer length,
final List<GATKSVVCFConstants.EvidenceTypes> evidence,
final List<String> algorithms,
final List<Allele> alleles,
final List<Genotype> genotypes,
final Map<String,Object> attributes,
final Set<String> filters,
final Double log10PError,
final SAMSequenceDictionary dictionary) {
this(id, contigA, positionA, strandA, contigB, positionB, strandB, type, cpxSubtype, cpxIntervals, length, algorithms, alleles, genotypes, attributes, filters, log10PError);
this(id, contigA, positionA, strandA, contigB, positionB, strandB, type, cpxSubtype, cpxIntervals, length, evidence, algorithms, alleles, genotypes, attributes, filters, log10PError);
validateCoordinates(dictionary);
}

Expand All @@ -94,6 +98,7 @@ protected SVCallRecord(final String id,
final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype,
final List<ComplexEventInterval> cpxIntervals,
final Integer length,
final List<GATKSVVCFConstants.EvidenceTypes> evidence,
final List<String> algorithms,
final List<Allele> alleles,
final List<Genotype> genotypes,
Expand All @@ -106,6 +111,7 @@ protected SVCallRecord(final String id,
Utils.nonNull(attributes);
Utils.nonNull(filters);
Utils.nonNull(cpxIntervals);
Utils.nonNull(evidence);
this.id = Utils.nonNull(id);
this.contigA = contigA;
this.positionA = positionA;
Expand All @@ -123,6 +129,7 @@ protected SVCallRecord(final String id,
this.genotypes = GenotypesContext.copy(genotypes).immutable();
this.attributes = validateAttributes(attributes);
this.length = inferLength(type, positionA, positionB, length);
this.evidence = evidence;
final Pair<Boolean, Boolean> strands = inferStrands(type, strandA, strandB);
this.strandA = strands.getLeft();
this.strandB = strands.getRight();
Expand Down Expand Up @@ -272,7 +279,8 @@ private boolean isCarrier(final Genotype genotype) {
}

// Otherwise, try to infer status if it's a biallelic CNV with a copy number call
final int copyNumber = VariantContextGetters.getAttributeAsInt(genotype, COPY_NUMBER_FORMAT, expectedCopyNumber);
final int copyNumber = VariantContextGetters.getAttributeAsInt(genotype, COPY_NUMBER_FORMAT,
VariantContextGetters.getAttributeAsInt(genotype, DEPTH_GENOTYPE_COPY_NUMBER_FORMAT, expectedCopyNumber));
if (type == GATKSVVCFConstants.StructuralVariantAnnotationType.DEL) {
return copyNumber < expectedCopyNumber;
} else if (type == GATKSVVCFConstants.StructuralVariantAnnotationType.DUP) {
Expand Down Expand Up @@ -370,6 +378,10 @@ public Integer getLength() {
return length;
}

public List<GATKSVVCFConstants.EvidenceTypes> getEvidence() {
return evidence;
}

public List<String> getAlgorithms() {
return algorithms;
}
Expand Down
35 changes: 27 additions & 8 deletions src/main/java/org/broadinstitute/hellbender/tools/sv/SVCallRecordUtils.java
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Original file line number Diff line number Diff line change
Expand Up @@ -18,6 +18,7 @@
import java.util.stream.Collectors;
import java.util.stream.Stream;

import static htsjdk.variant.vcf.VCFConstants.MISSING_VALUE_v4;
import static org.broadinstitute.hellbender.tools.sv.SVCallRecord.UNDEFINED_LENGTH;

public final class SVCallRecordUtils {
Expand Down Expand Up @@ -91,6 +92,9 @@ public static VariantContextBuilder getVariantBuilder(final SVCallRecord record)
&& record.getStrandA() != null && record.getStrandB() != null) {
builder.attribute(GATKSVVCFConstants.STRANDS_ATTRIBUTE, getStrandString(record));
}
if (!record.getEvidence().isEmpty()) {
builder.attribute(GATKSVVCFConstants.EVIDENCE, record.getEvidence());
}
if (!record.getFilters().isEmpty()) {
builder.filters(record.getFilters());
}
Expand Down Expand Up @@ -173,12 +177,12 @@ public static GenotypesContext populateGenotypesForMissingSamplesWithAlleles(fin
*/
public static SVCallRecord copyCallWithNewGenotypes(final SVCallRecord record, final GenotypesContext genotypes) {
return new SVCallRecord(record.getId(), record.getContigA(), record.getPositionA(), record.getStrandA(), record.getContigB(),
record.getPositionB(), record.getStrandB(), record.getType(), record.getComplexSubtype(), record.getComplexEventIntervals(), record.getLength(), record.getAlgorithms(), record.getAlleles(),
record.getPositionB(), record.getStrandB(), record.getType(), record.getComplexSubtype(), record.getComplexEventIntervals(), record.getLength(), record.getEvidence(), record.getAlgorithms(), record.getAlleles(),
genotypes, record.getAttributes(), record.getFilters(), record.getLog10PError());
}
public static SVCallRecord copyCallWithNewAttributes(final SVCallRecord record, final Map<String, Object> attr) {
return new SVCallRecord(record.getId(), record.getContigA(), record.getPositionA(), record.getStrandA(), record.getContigB(),
record.getPositionB(), record.getStrandB(), record.getType(), record.getComplexSubtype(), record.getComplexEventIntervals(), record.getLength(), record.getAlgorithms(), record.getAlleles(),
record.getPositionB(), record.getStrandB(), record.getType(), record.getComplexSubtype(), record.getComplexEventIntervals(), record.getLength(), record.getEvidence(), record.getAlgorithms(), record.getAlleles(),
record.getGenotypes(), attr, record.getFilters(), record.getLog10PError());
}

Expand Down Expand Up @@ -291,10 +295,10 @@ public static Stream<SVCallRecord> convertInversionsToBreakends(final SVCallReco
Utils.validateArg(record.isIntrachromosomal(), "Inversion " + record.getId() + " is not intrachromosomal");
final SVCallRecord positiveBreakend = new SVCallRecord(record.getId(), record.getContigA(),
record.getPositionA(), true, record.getContigB(), record.getPositionB(), true, GATKSVVCFConstants.StructuralVariantAnnotationType.BND, null,record.getComplexEventIntervals(), null,
record.getAlgorithms(), record.getAlleles(), record.getGenotypes(), record.getAttributes(), record.getFilters(), record.getLog10PError(), dictionary);
record.getEvidence(), record.getAlgorithms(), record.getAlleles(), record.getGenotypes(), record.getAttributes(), record.getFilters(), record.getLog10PError(), dictionary);
final SVCallRecord negativeBreakend = new SVCallRecord(record.getId(), record.getContigA(),
record.getPositionA(), false, record.getContigB(), record.getPositionB(), false, GATKSVVCFConstants.StructuralVariantAnnotationType.BND, null,record.getComplexEventIntervals(), null,
record.getAlgorithms(), record.getAlleles(), record.getGenotypes(), record.getAttributes(), record.getFilters(), record.getLog10PError(), dictionary);
record.getEvidence(), record.getAlgorithms(), record.getAlleles(), record.getGenotypes(), record.getAttributes(), record.getFilters(), record.getLog10PError(), dictionary);
return Stream.of(positiveBreakend, negativeBreakend);
}

Expand All @@ -319,8 +323,9 @@ public static SVCallRecord create(final VariantContext variant, boolean keepVari

final GATKSVVCFConstants.StructuralVariantAnnotationType type = inferStructuralVariantType(variant);
final GATKSVVCFConstants.ComplexVariantSubtype cpxSubtype = getComplexSubtype(variant);
final List<SVCallRecord.ComplexEventInterval> cpxIntervals = parseComplexIntervals(variant.getAttributeAsStringList(GATKSVVCFConstants.CPX_INTERVALS, null), dictionary);
final List<SVCallRecord.ComplexEventInterval> cpxIntervals = parseComplexIntervals(variant, dictionary);
final List<String> algorithms = getAlgorithms(variant);
final List<GATKSVVCFConstants.EvidenceTypes> evidence = getEvidence(variant);

final String strands;
if (type == GATKSVVCFConstants.StructuralVariantAnnotationType.DEL
Expand Down Expand Up @@ -375,12 +380,13 @@ public static SVCallRecord create(final VariantContext variant, boolean keepVari

final Map<String, Object> sanitizedAttributes = sanitizeAttributes(attributes);
return new SVCallRecord(id, contigA, positionA, strand1, contigB, positionB, strand2, type, cpxSubtype,
cpxIntervals, length, algorithms, variant.getAlleles(), variant.getGenotypes(), sanitizedAttributes,
cpxIntervals, length, evidence, algorithms, variant.getAlleles(), variant.getGenotypes(), sanitizedAttributes,
variant.getFilters(), log10PError);
}

private static List<SVCallRecord.ComplexEventInterval> parseComplexIntervals(final List<String> intervals, final SAMSequenceDictionary dictionary) {
return intervals.stream().map(i -> SVCallRecord.ComplexEventInterval.decode(i, dictionary)).toList();
private static List<SVCallRecord.ComplexEventInterval> parseComplexIntervals(final VariantContext variant, final SAMSequenceDictionary dictionary) {
return variant.getAttributeAsStringList(GATKSVVCFConstants.CPX_INTERVALS, null).stream()
.map(i -> SVCallRecord.ComplexEventInterval.decode(i, dictionary)).toList();
}

private static Map<String, Object> sanitizeAttributes(final Map<String, Object> attributes) {
Expand All @@ -402,6 +408,19 @@ private static Integer getLength(final VariantContext variant, final GATKSVVCFCo
return length;
}

public static List<GATKSVVCFConstants.EvidenceTypes> getEvidence(final VariantContext variant) {
Utils.nonNull(variant);
final List<String> value = variant.getAttributeAsStringList(GATKSVVCFConstants.EVIDENCE, null);
if (value == null) {
return Collections.emptyList();
} else {
return value.stream()
.filter(v -> v != null && !v.equals(MISSING_VALUE_v4))
.map(GATKSVVCFConstants.EvidenceTypes::valueOf)
.collect(Collectors.toList());
}
}

public static List<String> getAlgorithms(final VariantContext variant) {
Utils.nonNull(variant);
Utils.validateArg(variant.hasAttribute(GATKSVVCFConstants.ALGORITHMS_ATTRIBUTE), "Expected " + GATKSVVCFConstants.ALGORITHMS_ATTRIBUTE + " field for variant " + variant.getID());
Expand Down
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