270 lines
11 KiB
Java
270 lines
11 KiB
Java
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package org.broadinstitute.sting.oneoffprojects.walkers;
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import org.broad.tribble.vcf.VCFHeader;
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import org.broad.tribble.vcf.VCFHeaderLine;
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import org.broadinstitute.sting.commandline.Argument;
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import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
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import org.broadinstitute.sting.gatk.contexts.ReferenceContext;
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import org.broadinstitute.sting.gatk.contexts.variantcontext.Genotype;
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import org.broadinstitute.sting.gatk.contexts.variantcontext.VariantContext;
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import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
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import org.broadinstitute.sting.gatk.refdata.VariantContextAdaptors;
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import org.broadinstitute.sting.gatk.walkers.LocusWalker;
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import org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedArgumentCollection;
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import org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedGenotyperEngine;
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import org.broadinstitute.sting.gatk.walkers.varianteval.MendelianViolationEvaluator;
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import org.broadinstitute.sting.utils.GenomeLoc;
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import org.broadinstitute.sting.utils.SampleUtils;
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import org.broadinstitute.sting.utils.StingException;
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import org.broadinstitute.sting.utils.genotype.vcf.VCFUtils;
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import org.broadinstitute.sting.utils.genotype.vcf.VCFWriter;
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import java.util.*;
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/**
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* Takes in a VCF file for a trio (and optionally, bam files for some or all members) and classifies mendelian violations
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* as deNovo events, or opposite homozygotes, and includes additional information pertaining to event QC (size of
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* homozygous region in child and/or parents, whether a site is likely tri-allelic or not, etc)
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*
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* @Author chartl
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* @Date Jun 8, 2010
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*/
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public class MendelianViolationClassifier extends LocusWalker<MendelianViolationClassifier.MendelianViolation, VCFWriter> {
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@Argument(shortName="f",fullName="familyPattern",required=true,doc="Pattern for the family structure (usage: mom+dad=child)")
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String familyStr = null;
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/*
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****** PRIVATE CLASSES
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*/
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public class ExtendedTrioStructure extends MendelianViolationEvaluator.TrioStructure {
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public HashMap<String,HomozygosityRegion> homozygousRegions;
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public HashMap<String,Integer> homozygousRegionCounts;
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public ExtendedTrioStructure(String family) {
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MendelianViolationEvaluator.TrioStructure struct = MendelianViolationEvaluator.parseTrioDescription(family);
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this.child = struct.child;
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this.mom = struct.mom;
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this.dad = struct.dad;
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homozygousRegions = new HashMap<String,HomozygosityRegion>(3);
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homozygousRegionCounts = new HashMap<String,Integer>(3);
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homozygousRegions.put(child,null);
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homozygousRegions.put(mom,null);
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homozygousRegions.put(dad,null);
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homozygousRegionCounts.put(child,0);
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homozygousRegionCounts.put(mom,0);
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homozygousRegionCounts.put(dad,0);
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}
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}
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public class HomozygosityRegion {
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public GenomeLoc regionStart;
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public int callsWithinRegion;
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public HomozygosityRegion(GenomeLoc start) {
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regionStart = start;
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callsWithinRegion = 0;
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}
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}
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public class MendelianViolation {
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private VariantContext trio;
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public MendelianViolationType type;
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private HashMap<String,Object> newAttributes;
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public MendelianViolation(VariantContext context, MendelianViolationType violationType) {
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trio = context;
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type = violationType;
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newAttributes = new HashMap<String,Object>();
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newAttributes.put(MendelianInfoKey.ViolationType.getKey(),type);
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}
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public void addAttribute(String key, Object val) {
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newAttributes.put(key,val);
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}
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public VariantContext toVariantContext() {
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newAttributes.putAll(trio.getAttributes());
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return new VariantContext(trio.getName(),trio.getLocation(),trio.getAlleles(),trio.getGenotypes(),trio.getNegLog10PError(),trio.getFilters(),newAttributes);
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}
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public boolean siteIsFiltered() {
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return trio.isFiltered();
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}
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}
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/*
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********** PRIVATE ENUMS
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*/
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public enum MendelianViolationType {
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OPPOSITE_HOMOZYGOTE("oppositeHomozygote"),
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DE_NOVO_SNP("deNovoSNP"),
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NONE("none");
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private String infoString;
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MendelianViolationType(String typeName) {
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infoString=typeName;
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}
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public String toString() {
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return infoString;
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}
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}
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public enum MendelianInfoKey {
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ViolationType("MVT","String","\"The Mendelian violation type\""),
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ParentalDeletion("deletedParent","String","\"The parent from whom the child (putatively) inherited a deletion at opposite homozygous sites\""),
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ChildHomozygosityRegion("CHR","Integer","\"An identifier for the region of homozygosity in the child in which the opposite homozygote is located\""),
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ChildHomozygosityRegionSize("CHRS","Integer","\"The size of the region of homozygosity in the child in which the opposite homozygote is located\""),
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OppositeHomozygotesInRegion("CHROH","Integer","\"The number of opposite-homozygotes located in the region of homozygosity\""),
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TriAllelicQuality("TriAlQ","Integer","\"The variant quality of the third allele at putative tri-allelic sites\""),
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TriAllelicBase("TriAlB","String","\"The third allele at putative tri-allelic sites\""),
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NumCallsInRegion("REGION_NCALLS","Integer","\"The number of SNP calls found in the homozygosity region\""),
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ParentHomozygosityRegion("PHR","String","\"An identifier for the parent, and the region number, for the homozygosity region where the deNovo SNP is located\""),
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ParentHomozygosityRegionSize("PHRS","Integer","\"The size of the parental homozygosity region where the deNovo SNP is located\""),
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DeNovoSNPsInRegion("PHRDN","Integer","\"The number of deNovo SNP events located in the same region of parental homozygosity where the deNovo SNP is located\""),
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ProportionOfParentAllele("PropParent","Double","\"The proportion of bases in the child that were the parent allele at deNovo SNP sites\"");
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String keyName;
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String valueType;
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String valueDescription;
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MendelianInfoKey(String keyStr,String infoType,String description) {
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keyName = keyStr;
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valueType = infoType;
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valueDescription = description;
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}
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public String toString() {
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return String.format("%s,%s,%s",keyName,valueType,valueDescription);
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}
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public String getKey() {
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return keyName;
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}
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}
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/*
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*********** PRIVATE DATA
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*/
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private ExtendedTrioStructure trioStructure;
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private UnifiedGenotyperEngine engine;
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private ArrayList<VariantContext> contextBuffer;
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/*
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*********** INITIALIZE
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*/
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public void initialize() {
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trioStructure = new ExtendedTrioStructure(familyStr);
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contextBuffer = new ArrayList<VariantContext>(5000);
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UnifiedArgumentCollection uac = new UnifiedArgumentCollection();
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uac.MIN_BASE_QUALTY_SCORE = 10;
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uac.MIN_MAPPING_QUALTY_SCORE = 10;
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uac.STANDARD_CONFIDENCE_FOR_CALLING = 30;
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engine = new UnifiedGenotyperEngine(getToolkit(),uac);
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}
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/*
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*********** REDUCE INIT
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*/
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public VCFWriter reduceInit() {
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VCFWriter writer = new VCFWriter(out);
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Set<VCFHeaderLine> hInfo = new HashSet<VCFHeaderLine>();
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hInfo.addAll(VCFUtils.getHeaderFields(getToolkit()));
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hInfo.add(new VCFHeaderLine("source", "OppositeHomozygoteClassifier"));
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for ( MendelianInfoKey key : EnumSet.allOf(MendelianInfoKey.class) ) {
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hInfo.add( new VCFHeaderLine("INFO",key.toString()));
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}
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VCFHeader vcfHeader = new VCFHeader(hInfo, SampleUtils.getUniqueSamplesFromRods(getToolkit()));
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writer.writeHeader(vcfHeader);
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return writer;
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}
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/*
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*********** MAP
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*/
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public MendelianViolation map(RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
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if ( tracker == null ) {
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return null;
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}
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return assessViolation(tracker.getVariantContext(ref,"trio", EnumSet.of(VariantContext.Type.SNP),ref.getLocus(),true),tracker,ref,context);
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}
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private MendelianViolation assessViolation(VariantContext varContext, RefMetaDataTracker tracker, ReferenceContext reference, AlignmentContext context) {
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MendelianViolation violation;
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if ( MendelianViolationEvaluator.isViolation(varContext,trioStructure) ) {
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if ( isDeNovo(varContext) ) {
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violation = assessDeNovo(varContext,tracker,reference,context);
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} else if ( isOppositeHomozygote(varContext) ) {
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violation = assessOppositeHomozygote(varContext,tracker,reference,context);
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} else {
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throw new StingException("Mendelian violation that is neither deNovo nor opposite homozygote. Should never see this.");
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}
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} else {
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violation = new MendelianViolation(varContext,MendelianViolationType.NONE);
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}
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return violation;
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}
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// Note, mendelian violation is guaranteed at this point; deNovo only happens at child het sites
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private boolean isDeNovo(VariantContext trio) {
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return trio.getGenotype(trioStructure.child).isHet();
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}
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// Note, mendelian violation is guaranteed at this point; technically we do not have to check this...but we are
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private boolean isOppositeHomozygote(VariantContext trio) {
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if ( trio.getGenotype(trioStructure.child).isHet() ) { // not valid at child het sites
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return false;
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} else if ( trio.getHetCount() > 1 ) { // child is not het, so if this is 2, mom and dad are both het, invalid
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return false;
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} else if ( trio.getGenotype(trioStructure.dad) == null || trio.getGenotype(trioStructure.mom) == null ) {
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return false;
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}
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return true;
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}
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private MendelianViolation assessDeNovo(VariantContext trio, RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
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// todo -- implement me
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return new MendelianViolation(trio,MendelianViolationType.DE_NOVO_SNP);
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}
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private MendelianViolation assessOppositeHomozygote(VariantContext trio, RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
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// todo -- implement me
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return new MendelianViolation(trio,MendelianViolationType.OPPOSITE_HOMOZYGOTE);
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}
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/*
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*********** REDUCE
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*/
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public VCFWriter reduce(MendelianViolation variant, VCFWriter writer) {
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if ( variant != null ) {
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if ( ! variant.siteIsFiltered() ) {
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// todo -- fill me in
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} else { /* just add filtered variants to output if they're wanted */
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contextBuffer.add(variant.toVariantContext());
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}
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}
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return writer;
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}
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/*
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********** ON TRAVERSAL DONE
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*/
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public void onTraversalDone(VCFWriter writer) {
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while ( contextBuffer.size() > 0 ) {
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VariantContext vc = contextBuffer.remove(0);
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writer.addRecord(VariantContextAdaptors.toVCF(vc,vc.getReference().getBases()[0]));
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}
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}
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}
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