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Bug fix in flow allele filtering #8775

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1 change: 1 addition & 0 deletions .gitignore
Original file line number Diff line number Diff line change
Expand Up @@ -44,3 +44,4 @@ funcotator_tmp

#Test generated dot files
test*.dot
.vscode/
Original file line number Diff line number Diff line change
Expand Up @@ -303,9 +303,11 @@ private List<Event> identifyBadAlleles(final List<Integer> collectedRPLs, final
//we then add alleles with high SOR. Note that amongh all allleles with the SOR higher than the SOR_THRESHOLD
//we will first filter the one with the lowest QUAL.
logger.debug(() -> String.format("SHA:: Have %d candidates with low QUAL", rplCount));
for (int i = sorIndices.length-1 ; (i >= 0) && (collectedSORs.get(sorIndices[i])>SOR_THRESHOLD) ; i--) {
if (!result.contains(alleles.get(sorIndices[i]))) {
result.add(alleles.get(sorIndices[i]));
for (int i = sorIndices.length-1 ; (i >= 0) ; i--) {
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ahh thats a nasty issue i see...

if (collectedSORs.get(sorIndices[i])>SOR_THRESHOLD){
if (!result.contains(alleles.get(sorIndices[i]))) {
result.add(alleles.get(sorIndices[i]));
}
}
}
logger.debug(() -> String.format("SHA:: Have %d candidates with high SOR", result.size() - rplCount));
Expand Down
Original file line number Diff line number Diff line change
Expand Up @@ -298,5 +298,70 @@ public void testNotFilterLoneWeakAllele(){

}

@Test //check that we filter strong allele with high SOR
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I think this test might test what you want here. I would recommend adding a unit test to the AlleleFiltering.identifyBadAlleles() (made package protected and marked with @VisibleForTesting) and constructing a specific case that triggers this bug and explaining that its capturing the state where the SOR and Qual based filtering sorting are out of step and you are still fitlering appropriately.

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@jamesemery - good idea, added test!

public void testFilterDistantHindelSor() {

// create haplotypes
List<Haplotype> haplotypeList = new ArrayList<>();
final byte[] fullReferenceWithPadding = "CAGGCATG".getBytes();
Haplotype haplotype = new Haplotype(fullReferenceWithPadding, true, 0, TextCigarCodec.decode("8M"));
haplotype.setGenomeLocation(new SimpleInterval("chr", 100, 108));
haplotype.setEventMap(EventMap.fromHaplotype(haplotype, fullReferenceWithPadding, 0));
haplotypeList.add(haplotype);

haplotype = new Haplotype("CAGGCATTG".getBytes(), false, 0, TextCigarCodec.decode("7M1I1M"));
haplotype.setGenomeLocation(new SimpleInterval("chr", 100, 109));

haplotype.setEventMap(EventMap.fromHaplotype(haplotype, fullReferenceWithPadding, 0));
haplotypeList.add(haplotype);
haplotype = new Haplotype("CAGGCATTTG".getBytes(), false, 0, TextCigarCodec.decode("7M2I1M"));
haplotype.setGenomeLocation(new SimpleInterval("chr", 100, 110));

haplotype.setEventMap(EventMap.fromHaplotype(haplotype, fullReferenceWithPadding, 0));
haplotypeList.add(haplotype);

AlleleList<Haplotype> haplotypes = new IndexedAlleleList<>(haplotypeList);
SampleList samples = new IndexedSampleList(Arrays.asList("sm1"));

List<GATKRead> readList = new ArrayList<>(30);
Map<String, List<GATKRead>> ebs = new HashMap<>();
ebs.put("sm1", readList);

for (int i = 0; i < 40; i++) {
readList.add(ArtificialReadUtils.createArtificialRead("20M"));
}


double[][] values = {
{ 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3,
0, 3, 0, 3, 0,
3 },
{ 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0, 3, 0,
3, 0, 3, 0, 3,
0 },
{ 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0, 0, 10, 0, 0,0,10,0,0,0,10,0,0,0}
};
for (int i = 0; i < 40; i++) {
if (i % 4 == 0) {
readList.get(i).setIsReverseStrand(true);
}
}

AlleleLikelihoods<GATKRead, Haplotype> lks = new AlleleLikelihoods<>(samples, haplotypes, ebs);
LikelihoodMatrix<GATKRead, Haplotype> lkm = lks.sampleMatrix(0);
for (int i = 0; i < lks.numberOfAlleles(); i++) {
for (int j = 0; j < lkm.evidenceCount(); j++) {
lkm.set(i, j, values[i][j]);
}
}

HaplotypeCallerArgumentCollection hcArgs = new HaplotypeCallerArgumentCollection();
HaplotypeCallerGenotypingEngine genotypingEngine = new HaplotypeCallerGenotypingEngine(hcArgs, samples,
!hcArgs.doNotRunPhysicalPhasing, false);

AlleleFiltering alleleFiltering = new AlleleFilteringHC(hcArgs, null, genotypingEngine);
AlleleLikelihoods<GATKRead, Haplotype> filtered_lks = alleleFiltering.filterAlleles(lks, 0, new HashSet<>());
Assert.assertEquals(filtered_lks.alleles(), haplotypeList.subList(0, 2));
}

}
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