simple walker that works off pre-computed tumor/normal genotyping calls (e.g. samtools pileup). Collects overal stats and also writes somatic variants into IGV-compatible bed file if asked to. NOT finished. NOT tested
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@819 348d0f76-0448-11de-a6fe-93d51630548a
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package org.broadinstitute.sting.playground.gatk.walkers;
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import java.io.BufferedOutputStream;
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import java.io.FileWriter;
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import java.io.OutputStream;
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import org.apache.log4j.Logger;
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import org.broadinstitute.sting.gatk.LocusContext;
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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.refdata.Genotype;
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import org.broadinstitute.sting.gatk.walkers.RefWalker;
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import org.broadinstitute.sting.gatk.walkers.Requires;
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import org.broadinstitute.sting.gatk.walkers.DataSource;
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import org.broadinstitute.sting.gatk.walkers.RMD;
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import org.broadinstitute.sting.playground.utils.GenotypingCallStats;
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import org.broadinstitute.sting.utils.GenotypeUtils;
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import org.broadinstitute.sting.utils.StingException;
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import org.broadinstitute.sting.utils.cmdLine.Argument;
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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 SomaticMutationFromGenotypeWalker extends RefWalker<SomaticMutationRecord, SomaticMutationRecord> {
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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="default_reference_calls",shortName="DRC",
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doc="If set, any position where the requested genotype subtype (variant_type) 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="Look for variants of specified type (POINT mutations or INDELs)",
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required=true)
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public String VTYPE_STR;
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@Argument(fullName="bed_out", shortName="BED", doc="Write somatic variants into the specified file in BED format",required=false) public java.io.File BED_OUT;
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private java.io.Writer bed_stream = null;
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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 SomaticMutationRecord map(RefMetaDataTracker rodData, char ref, LocusContext context) {
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// String outLine = new String(context.getLocation() + " REF: "+ref + " RODS:" + rodData.getAllRods().size());
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ReferenceOrderedDatum rodNormal = rodData.lookup("normal", null);
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ReferenceOrderedDatum rodTumor = rodData.lookup("tumor", null);
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ReferenceOrderedDatum rodRefseq = rodData.lookup("refseq", null);
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Genotype normal = GenotypeUtils.extractGenotype(rodNormal,VARIANT_TYPE, defCalls);
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Genotype tumor = GenotypeUtils.extractGenotype(rodTumor,VARIANT_TYPE,defCalls);
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SomaticMutationRecord r = new SomaticMutationRecord();
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if ( rodRefseq == null ) return r;
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out.println(context.getLocation() + " " + rodRefseq.toString() );
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if ( true ) return r;
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assessGenotype(normal,r.normal);
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assessGenotype(tumor, r.tumor);
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if ( r.normal.covered == 1 && r.tumor.covered == 1 ) r.mut.covered = 1;
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if ( r.normal.assessed == 1 && r.tumor.assessed == 1 ) r.mut.assessed = 1;
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else {
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if ( r.tumor.variant == 1 ) {
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if ( r.normal.covered == 0 ) r.tumor_variant_without_normal = 1; // normal is not even covered
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else if ( r.normal.assessed == 0 ) r.tumor_variant_without_confident_normal = 1; // normal is covered but can not make confident call
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}
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if ( r.normal.variant == 1 ) {
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if ( r.tumor.covered == 0 ) r.normal_variant_without_tumor = 1; // normal is not even covered
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else if ( r.tumor.assessed == 0 ) r.normal_variant_without_confident_tumor = 1; // normal is covered but can not make confident call
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}
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return r;
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}
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// both tumor and normal are assessed
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if ( r.normal.variant == 0 && r.tumor.variant == 0 ) {
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r.mut.ref = r.mut.consistent_ref = 1;
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return r;
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}
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// at least one sample has a confident variant call
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String n_allele1 = normal.getFWDAlleles().get(0);
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String n_allele2 = normal.getFWDAlleles().get(1);
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String t_allele1 = tumor.getFWDAlleles().get(0);
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String t_allele2 = tumor.getFWDAlleles().get(1);
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if ( r.normal.variant == 1 && r.tumor.variant == 1 ) {
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// germline variant
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r.germline = 1;
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if ( ! ( n_allele1.equals( t_allele1 ) && n_allele2.equals( t_allele2 ) ||
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n_allele1.equals( t_allele2 ) && n_allele2.equals( t_allele1 ) ) ) r.non_matching_germline = 1;
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return r;
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}
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if ( r.normal.variant == 1 && r.tumor.variant == 0 ) {
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// variant in normal, but not in tumor, what the hell?
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r.lost_variant = 1;
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return r;
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}
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// last possibility: variant in tumor but not in normal (both are assessed!)
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r.mut.variant = 1;
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if ( bed_stream != null ) {
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long stop = normal.getLocation().getStop();
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if ( stop < normal.getLocation().getStart() + 1 ) stop = normal.getLocation().getStart()+1;
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try {
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bed_stream.append(normal.getLocation().getContig()+"\t"+
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normal.getLocation().getStart() + "\t" +
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stop +"\t"+
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genotypeString(tumor));
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} catch ( Exception e ) {
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throw new StingException("Failed to write into BED output "+BED_OUT+": " + e.getMessage() );
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}
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}
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return r;
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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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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 SomaticMutationRecord reduce(SomaticMutationRecord value, SomaticMutationRecord sum) {
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return sum.add(value);
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}
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@Override
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public void initialize() {
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super.initialize();
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if ( BED_OUT != null ) {
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try {
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bed_stream = new java.io.BufferedWriter( new FileWriter(BED_OUT) );
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} catch ( Exception e ) {
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throw new StingException("Failed to initialize BED output "+BED_OUT+": " + e.getMessage() );
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}
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}
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VARIANT_TYPE = GenotypeUtils.VariantType.valueOf(VTYPE_STR.toUpperCase());
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}
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@Override
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public SomaticMutationRecord reduceInit() {
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return new SomaticMutationRecord();
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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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public void onTraversalDone(SomaticMutationRecord result) {
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if ( bed_stream != null ) {
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try {
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bed_stream.close();
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} catch ( Exception e ) {
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throw new StingException("Failed to close BED output file "+BED_OUT+": " + e.getMessage() );
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}
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}
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super.onTraversalDone(result);
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}
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}
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class SomaticMutationRecord {
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GenotypingCallStats normal;
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GenotypingCallStats tumor;
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GenotypingCallStats mut;
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int germline = 0;
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int non_matching_germline = 0;
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int tumor_variant_without_normal = 0;
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int tumor_variant_without_confident_normal = 0;
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int normal_variant_without_tumor = 0;
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int normal_variant_without_confident_tumor = 0;
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int lost_variant = 0;
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public SomaticMutationRecord() {
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normal = new GenotypingCallStats();
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tumor = new GenotypingCallStats();
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mut = new GenotypingCallStats();
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}
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public SomaticMutationRecord add(SomaticMutationRecord other) {
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normal.add(other.normal);
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tumor.add(other.tumor);
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mut.add(other.mut);
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germline += other.germline;
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non_matching_germline += other.non_matching_germline;
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tumor_variant_without_normal += other.tumor_variant_without_normal;
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tumor_variant_without_confident_normal += other.tumor_variant_without_confident_normal;
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normal_variant_without_tumor += other.normal_variant_without_tumor;
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normal_variant_without_confident_tumor += other.normal_variant_without_confident_tumor;
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lost_variant += other.lost_variant;
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return this;
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}
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}
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