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Handle CTX_INV subtype in SVAnnotate (#8693)
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@epiercehoffman
epiercehoffman committed Feb 15, 2024
1 parent bbc028b commit cfd4d87
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Showing 3 changed files with 48 additions and 13 deletions.
3 changes: 2 additions & 1 deletion 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 @@ -91,7 +91,8 @@ public enum ComplexVariantSubtype {
dDUP_iDEL,
INS_iDEL,
CTX_PP_QQ,
CTX_PQ_QP
CTX_PQ_QP,
CTX_INV
}

// not defined in output vcf header but used in internal id that is currently output in the ID column
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24 changes: 16 additions & 8 deletions src/main/java/org/broadinstitute/hellbender/tools/walkers/sv/SVAnnotateEngine.java
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Original file line number Diff line number Diff line change
Expand Up @@ -570,9 +570,9 @@ protected static List<SVSegment> parseComplexIntervals(final List<String> cpxInt
* protein-coding consequences
*/
@VisibleForTesting
protected static List<SVSegment> getComplexAnnotationIntervals(final List<SVSegment> cpxIntervals,
protected static ArrayList<SVSegment> getComplexAnnotationIntervals(final List<SVSegment> cpxIntervals,
final GATKSVVCFConstants.ComplexVariantSubtype complexType) {
final List<SVSegment> segments = new ArrayList<>(cpxIntervals.size());
final ArrayList<SVSegment> segments = new ArrayList<>(cpxIntervals.size());
final List<SimpleInterval> dupIntervals = new ArrayList<>(cpxIntervals.size());
SimpleInterval inversionIntervalToAdjust = null;
boolean keepSegment;
Expand Down Expand Up @@ -679,8 +679,8 @@ protected static List<SVSegment> getSVSegments(final VariantContext variant,
final int pos = variant.getStart();
final String chr2 = variant.getAttributeAsString(GATKSVVCFConstants.CONTIG2_ATTRIBUTE, null);
final int end2 = variant.getAttributeAsInt(GATKSVVCFConstants.END2_ATTRIBUTE, pos);
final List<String> cpxIntervals = variant.getAttributeAsStringList(GATKSVVCFConstants.CPX_INTERVALS, null);
if (overallSVType.equals(GATKSVVCFConstants.StructuralVariantAnnotationType.CPX)) {
final List<String> cpxIntervals = variant.getAttributeAsStringList(GATKSVVCFConstants.CPX_INTERVALS, null);
if (cpxIntervals.isEmpty()) {
throw new UserException("Complex (CPX) variant must contain CPX_INTERVALS INFO field");
}
Expand All @@ -695,14 +695,22 @@ protected static List<SVSegment> getSVSegments(final VariantContext variant,
new SimpleInterval(chrom, pos, pos + 1)));
}
} else if (overallSVType.equals(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX)) {
intervals = new ArrayList<>(2);
intervals.add(new SVSegment(overallSVType, new SimpleInterval(variant))); // CHROM:POS-POS+1
// annotate both breakpoints of translocation - CHR2:END2-END2+1
// if SVTYPE is CTX and CPX_TYPE is CTX_INV, add INV from CTX_INTERVALS
if (complexType == GATKSVVCFConstants.ComplexVariantSubtype.CTX_INV && !cpxIntervals.isEmpty()) {
intervals = getComplexAnnotationIntervals(parseComplexIntervals(cpxIntervals), complexType);
} else {
intervals = new ArrayList<>(2);
}
// annotate POS and END separately in case END != POS+1, such as in the case of CTX_INV
intervals.add(new SVSegment(overallSVType, new SimpleInterval(chrom, pos, pos)));
intervals.add(new SVSegment(overallSVType, new SimpleInterval(chrom, variant.getEnd(), variant.getEnd())));
// annotate breakpoints of translocation on CHR2 - END2 and END2+1
// TODO: update if POS2 is added to accommodate complex translocations
if (chr2 == null) {
throw new UserException("Translocation (CTX) variant represented as a single record must contain CHR2 INFO field");
}
intervals.add(new SVSegment(overallSVType,
new SimpleInterval(chr2, end2, end2 + 1)));
intervals.add(new SVSegment(overallSVType, new SimpleInterval(chr2, end2, end2)));
intervals.add(new SVSegment(overallSVType, new SimpleInterval(chr2, end2 + 1, end2 + 1)));
} else if (overallSVType.equals(GATKSVVCFConstants.StructuralVariantAnnotationType.BND)){
intervals = new ArrayList<>(2);
final int svLen = variant.getAttributeAsInt(GATKSVVCFConstants.SVLEN, 0);
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34 changes: 30 additions & 4 deletions src/test/java/org/broadinstitute/hellbender/tools/walkers/sv/SVAnnotateEngineUnitTest.java
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Original file line number Diff line number Diff line change
Expand Up @@ -481,7 +481,8 @@ public Object[][] getComplexSubtypes() {
{ GATKSVVCFConstants.ComplexVariantSubtype.dDUP_iDEL, true },
{ GATKSVVCFConstants.ComplexVariantSubtype.INS_iDEL, false },
{ GATKSVVCFConstants.ComplexVariantSubtype.CTX_PP_QQ, false },
{ GATKSVVCFConstants.ComplexVariantSubtype.CTX_PQ_QP, false }
{ GATKSVVCFConstants.ComplexVariantSubtype.CTX_PQ_QP, false },
{ GATKSVVCFConstants.ComplexVariantSubtype.CTX_INV, false }
};
}

Expand Down Expand Up @@ -564,8 +565,10 @@ public Object[][] getSVTypesAndSegmentsTestData() {
GATKSVVCFConstants.ComplexVariantSubtype.CTX_PP_QQ,
GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
createListOfSVSegments(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval[]{ new SimpleInterval("chr2", 86263976, 86263977),
new SimpleInterval("chr19", 424309, 424310) }),
new SimpleInterval[]{ new SimpleInterval("chr2", 86263976, 86263976),
new SimpleInterval("chr2", 86263977, 86263977),
new SimpleInterval("chr19", 424309, 424309),
new SimpleInterval("chr19", 424310, 424310) }),
null },
{ createVariantContext("chr2", 86263976, 86263976, null, 424309, "G",
"G]chr19:424309]", null, null,"CTX_PP/QQ", null),
Expand All @@ -575,12 +578,28 @@ public Object[][] getSVTypesAndSegmentsTestData() {
new SimpleInterval("chr2", 86263976, 86263976))),
null},
{ createVariantContext("chr2", 86263977, 86263977, null, 424309, "A",
"[chr19:424310[A", null, null, "CTX_PP/QQ", null),
"[chr19:424310[A", -1, null, "CTX_PP/QQ", null),
GATKSVVCFConstants.ComplexVariantSubtype.CTX_PP_QQ,
GATKSVVCFConstants.StructuralVariantAnnotationType.BND,
Arrays.asList(new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval("chr2", 86263977, 86263977))),
null },
{ createVariantContext("chr4", 21923233, 22506191, "chr8", 107912008, "N",
"<CTX>", null, null, "CTX_INV",
Collections.singletonList("INV_chr4:21923233-22506191")),
GATKSVVCFConstants.ComplexVariantSubtype.CTX_INV,
GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
Arrays.asList(new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.INV,
new SimpleInterval("chr4", 21923233, 22506191)),
new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval("chr4", 21923233, 21923233)),
new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval("chr4", 22506191, 22506191)),
new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval("chr8", 107912008, 107912008)),
new SVAnnotateEngine.SVSegment(GATKSVVCFConstants.StructuralVariantAnnotationType.CTX,
new SimpleInterval("chr8", 107912009, 107912009)) ),
null },
{ createVariantContext("chr2", 205522308, 205522384, "chr2", null, "N",
"<INV>", 76, null, null, null),
null,
Expand Down Expand Up @@ -862,6 +881,13 @@ public Object[][] getAnnotateStructuralVariantTestData() {
createAttributesMap(
Arrays.asList(GATKSVVCFConstants.PROMOTER,GATKSVVCFConstants.INTERGENIC),
Arrays.asList("EMMA2", true)) },
// CTX_INV - this test case is not interchromosomal because the test GTF only has chr1
{ createVariantContext("chr1", 10, 1010, "chr1", 2300, null,
"<CTX>", -1, null, "CTX_INV", Arrays.asList("INV_chr1:10-1010")),
createAttributesMap(
Arrays.asList(GATKSVVCFConstants.INV_SPAN, GATKSVVCFConstants.NONCODING_SPAN,
GATKSVVCFConstants.LOF, GATKSVVCFConstants.INTERGENIC),
Arrays.asList("EMMA1", "DNase", "EMMA2", false))},
// check annotate promoter for all segments in multi-segment SV
{ createVariantContext("chr1", 30, 30, "chr1", 3030, null,
"<BND>", null, "-+", null, null),
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