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Adding TransmittedSingleton annotation and adding quality threshold a… #8329
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144 changes: 144 additions & 0 deletions
144
...main/java/org/broadinstitute/hellbender/tools/walkers/annotator/TransmittedSingleton.java
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| package org.broadinstitute.hellbender.tools.walkers.annotator; | ||
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| import com.google.common.annotations.VisibleForTesting; | ||
| import htsjdk.variant.variantcontext.Allele; | ||
| import htsjdk.variant.variantcontext.VariantContext; | ||
| import htsjdk.variant.vcf.VCFConstants; | ||
| import org.apache.logging.log4j.LogManager; | ||
| import org.apache.logging.log4j.Logger; | ||
| import org.broadinstitute.barclay.argparser.ExperimentalFeature; | ||
| import org.broadinstitute.barclay.help.DocumentedFeature; | ||
| import org.broadinstitute.hellbender.engine.GATKPath; | ||
| import org.broadinstitute.hellbender.engine.ReferenceContext; | ||
| import org.broadinstitute.hellbender.utils.Utils; | ||
| import org.broadinstitute.hellbender.utils.genotyper.AlleleLikelihoods; | ||
| import org.broadinstitute.hellbender.utils.help.HelpConstants; | ||
| import org.broadinstitute.hellbender.utils.logging.OneShotLogger; | ||
| import org.broadinstitute.hellbender.utils.read.GATKRead; | ||
| import org.broadinstitute.hellbender.utils.samples.Trio; | ||
| import org.broadinstitute.hellbender.utils.variant.GATKVCFConstants; | ||
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| import java.util.*; | ||
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| /** | ||
| * Existence of a transmitted or non-transmitted singleton in at least one of the given families | ||
| * | ||
| * <p>This annotation uses the genotype information from individuals in family trios to identify transmitted and non-transmitted singletons and the sample(s) in which they occur. | ||
| * Transmitted singletons occur at sites in a cohort where the allele count is two and these two alleles occur in one parent and the child of a trio. A non-transmitted singleton | ||
| * are sites with an allele count of one and this one allele occurs in a parent, but not the child of a trio. In both cases the other parent must have a high quality hom ref call. | ||
| * | ||
| * <h3>Caveats</h3> | ||
| * <ul> | ||
| * <li>The calculation assumes that the organism is diploid.</li> | ||
| * <li>This annotation requires a valid pedigree file.</li> | ||
| * <li>This annotation is only valid for trios, not quads or other more complicated family structures.</li> | ||
| * <li>Only reports possible singletons for families where each of the three samples has high GQ (>20) and high depth (>20)</li> | ||
| * <li>Only reports possible singletons at sites with a Call Rate greater than 90% (meaning less than 10% of the samples at the given site were no-calls)</li> | ||
| * </ul> | ||
| */ | ||
| @DocumentedFeature(groupName= HelpConstants.DOC_CAT_ANNOTATORS, groupSummary=HelpConstants.DOC_CAT_ANNOTATORS_SUMMARY, summary="Existence of a transmitted (or non-transmitted) singleton in at least one of the given families (transmittedSingleton, nonTransmittedSingleton)") | ||
| public final class TransmittedSingleton extends PedigreeAnnotation implements InfoFieldAnnotation { | ||
| protected final Logger warning = LogManager.getLogger(this.getClass()); | ||
| private final OneShotLogger oneShotLogger = new OneShotLogger(this.getClass()); | ||
| private Set<Trio> trios; | ||
| private final int HI_GQ_THRESHOLD = 20; | ||
| private final int HI_DP_THRESHOLD = 20; | ||
| private final double CALL_RATE_THRESHOLD = 0.90; | ||
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| @VisibleForTesting | ||
| public TransmittedSingleton(final Set<Trio> trios) { | ||
| super((Set<String>) null); | ||
| this.trios = Collections.unmodifiableSet(new LinkedHashSet<>(trios)); | ||
| } | ||
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| public TransmittedSingleton(final GATKPath pedigreeFile){ | ||
| super(pedigreeFile); | ||
| } | ||
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| public TransmittedSingleton(){ | ||
| super((Set<String>) null); | ||
| } | ||
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| private Set<Trio> initializeAndGetTrios() { | ||
| if (trios == null) { | ||
| trios = getTrios(); | ||
| } | ||
| final long numOfTrios = trios.stream().map(trio -> trio.getMother().getFamilyID()).count(); | ||
| if (numOfTrios == 0) { | ||
| oneShotLogger.warn("Submitted pedigree has no trios. TransmittedSingleton annotation will not be calculated."); | ||
| } else if (numOfTrios != trios.stream().map(trio -> trio.getMother().getFamilyID()).distinct().count()) { | ||
| oneShotLogger.warn("Submitted pedigree has non-trio families. TransmittedSingleton annotation is only valid for trios. Non-trio families (such as quads) will be ignored."); | ||
| } | ||
| return trios; | ||
| } | ||
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| @Override | ||
| void validateArguments(Collection<String> founderIds, GATKPath pedigreeFile) { | ||
| String warningString = validateArgumentsWhenPedigreeRequired(founderIds, pedigreeFile); | ||
| if (warningString != null) { | ||
| warning.warn(warningString); | ||
| } | ||
| } | ||
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| @Override | ||
| public List<String> getKeyNames() { | ||
| return Arrays.asList(GATKVCFConstants.TRANSMITTED_SINGLETON, GATKVCFConstants.NON_TRANSMITTED_SINGLETON); | ||
| } | ||
| @Override | ||
| public Map<String, Object> annotate(final ReferenceContext ref, | ||
| final VariantContext vc, | ||
| final AlleleLikelihoods<GATKRead, Allele> likelihoods) { | ||
| Utils.nonNull(vc); | ||
| Set<Trio> trioSet = initializeAndGetTrios(); | ||
| if (!vc.isBiallelic() || trioSet.isEmpty()) { | ||
| return Collections.emptyMap(); | ||
| } | ||
| long highQualCalls = vc.getGenotypes().stream().filter(gt -> gt.getGQ() > HI_GQ_THRESHOLD).count(); | ||
| if ((double) highQualCalls / vc.getNSamples() < CALL_RATE_THRESHOLD) { | ||
| return Collections.emptyMap(); | ||
| } | ||
| final List<String> transmittedSingletonParent = new ArrayList<>(); | ||
| final List<String> nonTransmittedSingletonParent = new ArrayList<>(); | ||
| for (final Trio trio : trioSet) { | ||
| if (vc.isBiallelic() && | ||
| contextHasTrioGQs(vc, trio)) { | ||
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| final boolean oneParentHasAllele = (vc.getGenotype(trio.getMaternalID()).isHet() && vc.getGenotype(trio.getPaternalID()).isHomRef()) || (vc.getGenotype(trio.getMaternalID()).isHomRef() && vc.getGenotype(trio.getPaternalID()).isHet()); | ||
| final String matchingParentId = vc.getGenotype(trio.getMaternalID()).isHet() ? trio.getMaternalID() : trio.getPaternalID(); | ||
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| final boolean momIsHighGQ = vc.getGenotype(trio.getMaternalID()).getGQ() >= HI_GQ_THRESHOLD; | ||
| final boolean dadIsHighGQ = vc.getGenotype(trio.getPaternalID()).getGQ() >= HI_GQ_THRESHOLD; | ||
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| final boolean childIsHighGQHet = vc.getGenotype(trio.getChildID()).isHet() && vc.getGenotype(trio.getChildID()).getGQ() >= HI_GQ_THRESHOLD; | ||
| final boolean childIsHighGQHomRef = vc.getGenotype(trio.getChildID()).isHomRef() && vc.getGenotype(trio.getChildID()).getGQ() >= HI_GQ_THRESHOLD; | ||
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| final boolean childIsHighDepth = vc.getGenotype(trio.getChildID()).getDP() >= HI_DP_THRESHOLD; | ||
| final boolean momIsHighDepth = vc.getGenotype(trio.getChildID()).getDP() >= HI_DP_THRESHOLD; | ||
| final boolean dadIsHighDepth = vc.getGenotype(trio.getChildID()).getDP() >= HI_DP_THRESHOLD; | ||
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| //TODO: This only works for trios (not quads or other more complicated family structures that would make the AC>2) | ||
| if (childIsHighDepth && momIsHighDepth && dadIsHighDepth && | ||
| vc.getAttributeAsInt(VCFConstants.ALLELE_COUNT_KEY, 0) == 2 && | ||
| childIsHighGQHet && oneParentHasAllele && momIsHighGQ && dadIsHighGQ) { | ||
| transmittedSingletonParent.add(matchingParentId); | ||
| } | ||
| //TODO: This only works for trios (not quads or other more complicated family structures that would make the AC>1) | ||
| if (childIsHighDepth && momIsHighDepth && dadIsHighDepth && | ||
| vc.getAttributeAsInt(VCFConstants.ALLELE_COUNT_KEY, 0) == 1 && | ||
| childIsHighGQHomRef && momIsHighGQ && dadIsHighGQ) { | ||
| nonTransmittedSingletonParent.add(matchingParentId); | ||
| } | ||
| } | ||
| } | ||
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| final Map<String, Object> attributeMap = new LinkedHashMap<>(1); | ||
| if (!transmittedSingletonParent.isEmpty()) { | ||
| attributeMap.put(GATKVCFConstants.TRANSMITTED_SINGLETON, transmittedSingletonParent); | ||
| } | ||
| if (!nonTransmittedSingletonParent.isEmpty()) { | ||
| attributeMap.put(GATKVCFConstants.NON_TRANSMITTED_SINGLETON, nonTransmittedSingletonParent); | ||
| } | ||
| return attributeMap; | ||
| } | ||
| } |
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Generally these are captialized... i don't know if this breaks already run samples however...
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I was trying to follow the PossibleDeNovo convention which has hiConfDeNovo and loConfDeNovo. Those have been in production a long time (unlike transmittedSingleton), so I'm hesitant to change them. What do you think?
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This is low priority and you know better than i do. Feel free to ignore this comment I you like.