247 lines
9.8 KiB
Java
247 lines
9.8 KiB
Java
package org.broadinstitute.sting.playground.gatk.walkers;
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import org.apache.log4j.Logger;
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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.refdata.Genotype;
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import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
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import org.broadinstitute.sting.gatk.refdata.ReferenceOrderedDatum;
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import org.broadinstitute.sting.gatk.walkers.RefWalker;
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import org.broadinstitute.sting.playground.utils.GenotypingCallStats;
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import org.broadinstitute.sting.playground.utils.TrioConcordanceRecord;
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import org.broadinstitute.sting.utils.GenotypeUtils;
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import org.broadinstitute.sting.utils.cmdLine.Argument;
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import java.util.List;
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//@Requires(value=DataSource.REFERENCE,referenceMetaData={@RMD(name="mother",type=rodSAMPileup.class),
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// @RMD(name="father",type=rodSAMPileup.class),
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// @RMD(name="daughter",type=rodSAMPileup.class)})
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public class MendelianInheritanceWalker extends RefWalker<TrioConcordanceRecord, TrioConcordanceRecord> {
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@Argument(fullName="point_consensus_cutoff", shortName="XPC", doc="confidence cutoff for consensus in point genotype", required=true ) public Double POINT_CONS_CUTOFF;
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@Argument(fullName="point_variant_cutoff", shortName="XPV", doc="confidence cutoff for variant (snp) in point genotype", required=true ) public Double POINT_VAR_CUTOFF;
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@Argument(fullName="indel_consensus_cutoff", shortName="XIC", doc="confidence cutoff for consensus in indel genotype", required=true ) public Double INDEL_CONS_CUTOFF;
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@Argument(fullName="indel_variant_cutoff", shortName="XIV", doc="confidence cutoff for variant (snp) in indel genotype", required=true ) public Double INDEL_VAR_CUTOFF;
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@Argument(fullName="log_concordant", shortName="LC",doc="If set, all trio-concordant sites will be logged at level INFO") public boolean LOG_CONCORDANT;
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@Argument(fullName="log_discordant", shortName="LD",doc="If set, all trio-discordant sites will be logged at level INFO") public boolean LOG_DISCORDANT;
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@Argument(fullName="default_reference_calls",shortName="DRC",
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doc="If set, any position where the specified genotype is NOT explicitly specified, while the other is provided, is considered to be an implicit confident 'reference' (no-indel or no-snp) call")
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public boolean defCalls;
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@Argument(fullName="variant_type",
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shortName="VT",
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doc="Assess concordance for the variants of the specified type, INDEL or POINT. If genotype track(s) provide both types, the requested one will be selected",
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required=true)
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public String VTYPE_STR;
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private static Logger logger = Logger.getLogger(MendelianInheritanceWalker.class);
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private final static String star = new String("*");
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private GenotypeUtils.VariantType VARIANT_TYPE;
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@Override
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public TrioConcordanceRecord map(RefMetaDataTracker rodData, ReferenceContext ref, AlignmentContext context) {
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// String outLine = new String(context.getLocation() + " REF: "+ref + " RODS:" + rodData.getAllRods().size());
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ReferenceOrderedDatum rodMom = rodData.lookup("mother", null);
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ReferenceOrderedDatum rodDad = rodData.lookup("father", null);
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ReferenceOrderedDatum rodKid = rodData.lookup("daughter", null);
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Genotype mom = GenotypeUtils.extractGenotype(rodMom,VARIANT_TYPE,defCalls);
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Genotype dad = GenotypeUtils.extractGenotype(rodDad,VARIANT_TYPE,defCalls);
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Genotype kid = GenotypeUtils.extractGenotype(rodKid,VARIANT_TYPE,defCalls);
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return assessGenotypesInTrio(mom, dad, kid);
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}
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/**
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* @Override
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* @see org.broadinstitute.sting.gatk.walkers.Walker#initialize()
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*/
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public void initialize() {
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super.initialize();
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VARIANT_TYPE = GenotypeUtils.VariantType.valueOf(VTYPE_STR.toUpperCase());
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};
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/** Takes a single genotype object and returns properly filled new assessment object (covered/assessed/ref/variant set to 0/1
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* according to what the genotype says)
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* @param g
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* @return
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*/
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protected GenotypingCallStats assessGenotype(Genotype g, GenotypingCallStats stats) {
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if ( g != null ) stats.covered = 1;
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if ( hasCall(g)) {
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stats.assessed = 1;
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if ( g.isReference() ) stats.ref = 1;
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else {
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stats.variant = 1;
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if ( ! g.isBiallelic() ) stats.non_biallelic_variant = 1;
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}
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}
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return stats;
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}
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public TrioConcordanceRecord assessGenotypesInTrio(Genotype gMom, Genotype gDad, Genotype gKid) {
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TrioConcordanceRecord t = new TrioConcordanceRecord();
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// String outLine = new String(context.getLocation() + " REF: "+ref + " RODS:" + rodData.getAllRods().size());
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// first get separate stats on each individual
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assessGenotype(gMom,t.mom);
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assessGenotype(gDad,t.dad);
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assessGenotype(gKid,t.kid);
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// if ( hasCall(mom) && mom.isIndel() ) System.out.println("GOT INDEL: "+mom.toString());
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if ( t.mom.covered == 0 || t.dad.covered == 0 || t.kid.covered== 0 ) return t; // current position is not covered in at least one individual, there's nothing else to do
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t.trio.covered = 1; // ok, base covered in a trio (e.g. in all individuals)
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if ( t.mom.assessed != 0 && t.dad.assessed != 0 && t.kid.assessed != 0 ) {
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t.trio.assessed = 1; // assessed in trio = assessed in each individual
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} else return t; // at least one individual is not assessed, nothing left to do
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// we are here only if everyone is assessed
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// NOTE: "consistent_ref" in individuals is counted only when all 3 are assessed AND all 3 are ref (i.e. ref call in a trio)
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if( gMom.isReference() && gDad.isReference() && gKid.isReference() ) { // everyone is a ref
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t.trio.ref = t.trio.consistent_ref = 1;
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t.mom.consistent_ref = 1;
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t.dad.consistent_ref = 1;
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t.kid.consistent_ref = 1;
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return t; // done
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}
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// by now we know that there's a variant in at least one of the individuals
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t.trio.variant = 1;
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if ( t.mom.non_biallelic_variant == 1 || t.dad.non_biallelic_variant == 1 || t.kid.non_biallelic_variant == 1 ) {
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t.trio.non_biallelic_variant = 1;
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return t;
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}
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String kid_allele_1 = gKid.getFWDAlleles().get(0);
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String kid_allele_2 = gKid.getFWDAlleles().get(1);
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List<String> mom_alleles = gMom.getFWDAlleles();
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List<String> dad_alleles = gDad.getFWDAlleles();
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// warning: no special processing for X/Y chromosomes yet; not an issue for daughter
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if ( mom_alleles.contains(kid_allele_1) && dad_alleles.contains(kid_allele_2) ||
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mom_alleles.contains(kid_allele_2) && dad_alleles.contains(kid_allele_1) ) {
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t.trio.consistent_variant = 1;
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if ( ! gMom.isReference() ) {
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t.mom.consistent_variant = 1 ;
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if ( ! gKid.isReference() ) t.mom_passed_variant = 1;
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}
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if ( ! gDad.isReference() ) {
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t.dad.consistent_variant = 1 ;
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if ( ! gKid.isReference() ) t.dad_passed_variant = 1;
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}
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if ( ! gKid.isReference() ) t.kid.consistent_variant = 1 ;
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if ( LOG_CONCORDANT ) {
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logger.info("consistent variant at "+gMom.getLocation() +
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"("+gMom.getFWDRefBases()+") mom: " + genotypeString(gMom) + " dad: " +
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genotypeString(gDad) + " kid: " + genotypeString(gKid)
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);
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}
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} else {
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// we are inconsistent. let's see what happened:
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t.trio.inconsistent_variant = 1;
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if ( ! gMom.isReference() ) t.mom.inconsistent_variant = 1 ;
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if ( ! gDad.isReference() ) t.dad.inconsistent_variant = 1 ;
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if ( ! gKid.isReference() ) t.kid.inconsistent_variant = 1;
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if ( gKid.isReference() && ( ! gMom.isReference() && gMom.isHom() || ! gDad.isReference() && gDad.isHom() ) ) t.missing_variant_in_kid = 1;
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if ( ! gKid.isReference() && gMom.isReference() && gDad.isReference() ) t.missing_variant_in_parents = 1;
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if ( ! gKid.isReference() && ( ! gMom.isReference() || ! gDad.isReference() ) ) t.nonmatching_variant_in_kid = 1;
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if ( LOG_DISCORDANT ) {
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logger.info("inconsistent variant at "+gMom.getLocation() +
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"("+gMom.getFWDRefBases()+") mom: " + genotypeString(gMom) + " dad: " +
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genotypeString(gDad) + " kid: " + genotypeString(gKid)
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);
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}
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}
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return t;
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}
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protected String alleleString(Genotype g, int n) {
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if ( g.getFWDAlleles().get(n).length() == 0 ) return star;
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return g.getFWDAlleles().get(n);
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}
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protected String genotypeString(Genotype g) {
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return alleleString(g, 0) +"/"+alleleString(g, 1);
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}
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@Override
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public TrioConcordanceRecord reduce(TrioConcordanceRecord value, TrioConcordanceRecord sum) {
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return sum.add(value);
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}
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@Override
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public TrioConcordanceRecord reduceInit() {
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return new TrioConcordanceRecord();
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}
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boolean hasCall(Genotype g) {
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if ( g == null ) return false; // there's no call if there's no rod data available, duh!
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if ( g.isReference() ) {
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if ( g.isPointGenotype() ) return g.getConsensusConfidence() >= POINT_CONS_CUTOFF ;
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else return g.getConsensusConfidence() >= INDEL_CONS_CUTOFF ;
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}
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else { // it's a variant
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if ( g.isPointGenotype() ) return g.getVariantConfidence() >= POINT_VAR_CUTOFF ;
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else return g.getVariantConfidence() >= INDEL_VAR_CUTOFF ;
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}
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}
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/*
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protected String shortLine(Genotype av) {
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if ( av == null ) return new String( "<NULL>");
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if ( av.isReference() ) return new String ("*");
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List<String> alleles = av.getFWDAlleles();
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if ( av.isSNP() ) {
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if ( alleles.get(0).charAt(0) == av.getRef() ) return alleles.get(1);
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else return alleles.get(0);
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}
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if ( av.isInsertion() ) {
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if ( alleles.get(0).length() == 0 ) return new String('+'+alleles.get(1));
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else return new String('+'+alleles.get(0));
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}
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if ( av.isDeletion() ) {
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if ( alleles.get(0).length() == 0 ) return new String ('-'+alleles.get(0));
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else return new String('-'+alleles.get(1));
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}
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if ( av.isIndel() ) {
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return new String('?'+alleles.get(0));
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}
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return new String("<missing data!!!>");
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}
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*/
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}
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