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* Genotypes any number of gVCF files that were produced by the Haplotype Caller into a single joint VCF file.

*

* <p>

* GenotypeGVCFs merges gVCF records that were produced as part of the reference model-based variant discovery pipeline (see documentation for more details) using

* the '-ERC GVCF' or '-ERC BP_RESOLUTION' mode of the HaplotypeCaller.  This tool performs the multi-sample joint aggregation

* step and merges the records together in a sophisticated manner.

*

* At all positions of the target, this tool will combine all spanning records, produce correct genotype likelihoods,

* re-genotype the newly merged record, and then re-annotate it.

*

* Note that this tool cannot work with just any gVCF files - they must have been produced with the HaplotypeCaller,

* which uses a sophisticated reference model to produce accurate genotype likelihoods for every position in the target.

*

* <h3>Input</h3>

* <p>

* One or more Haplotype Caller gVCFs to genotype.

* </p>

*

* <h3>Output</h3>

* <p>

* A combined, genotyped VCF.

* </p>

*

* <h3>Examples</h3>

* <pre>

* java -Xmx2g -jar GenomeAnalysisTK.jar \

*   -R ref.fasta \

*   -T GenotypeGVCFs \

*   --variant gvcf1.vcf \

*   --variant gvcf2.vcf \

*   -o output.vcf

* </pre>

*

*/

    /**

     * The gVCF files to merge together

     */

    @Input(fullName="variant", shortName = "V", doc="One or more input gVCF files", required=true)

    public List<RodBindingCollection<VariantContext>> variantCollections;

    final private List<RodBinding<VariantContext>> variants = new ArrayList<>();

    @Output(doc="File to which variants should be written")

    protected VariantContextWriter vcfWriter = null;

    @Argument(fullName="includeNonVariantSites", shortName="allSites", doc="Include loci found to be non-variant after genotyping", required=false)

    public boolean INCLUDE_NON_VARIANTS = false;

    @ArgumentCollection

    public GenotypeCalculationArgumentCollection genotypeArgs = new GenotypeCalculationArgumentCollection();

    /**

     * Which annotations to recompute for the combined output VCF file.

     */

    @Advanced

    @Argument(fullName="annotation", shortName="A", doc="One or more specific annotations to recompute.  The single value 'none' removes the default annotations", required=false)

    protected List<String> annotationsToUse = new ArrayList<>(Arrays.asList(new String[]{"InbreedingCoeff", "FisherStrand", "QualByDepth", "ChromosomeCounts", "GenotypeSummaries", "StrandOddsRatio"}));

    /**

     * The rsIDs from this file are used to populate the ID column of the output.  Also, the DB INFO flag will be set when appropriate. Note that dbSNP is not used in any way for the calculations themselves.

     */

    @ArgumentCollection

    protected DbsnpArgumentCollection dbsnp = new DbsnpArgumentCollection();

    public RodBinding<VariantContext> getDbsnpRodBinding() { return dbsnp.dbsnp; }

    // the genotyping engine

    private UnifiedGenotypingEngine genotypingEngine;

    // the annotation engine

    private VariantAnnotatorEngine annotationEngine;

    public List<RodBinding<VariantContext>> getCompRodBindings() { return Collections.emptyList(); }

    public RodBinding<VariantContext> getSnpEffRodBinding() { return null; }

    public List<RodBinding<VariantContext>> getResourceRodBindings() { return Collections.emptyList(); }

    public boolean alwaysAppendDbsnpId() { return false; }

    public void initialize() {

        // collect the actual rod bindings into a list for use later

        for ( final RodBindingCollection<VariantContext> variantCollection : variantCollections )

            variants.addAll(variantCollection.getRodBindings());

        final GenomeAnalysisEngine toolkit = getToolkit();

        final Map<String, VCFHeader> vcfRods = GATKVCFUtils.getVCFHeadersFromRods(toolkit, variants);

        final SampleList samples = new IndexedSampleList(SampleUtils.getSampleList(vcfRods, GATKVariantContextUtils.GenotypeMergeType.REQUIRE_UNIQUE));

        // create the genotyping engine

        genotypingEngine = new UnifiedGenotypingEngine(createUAC(), samples, toolkit.getGenomeLocParser(), GeneralPloidyFailOverAFCalculatorProvider.createThreadSafeProvider(toolkit, genotypeArgs, logger),

                toolkit.getArguments().BAQMode);

        // create the annotation engine

        annotationEngine = new VariantAnnotatorEngine(Arrays.asList("none"), annotationsToUse, Collections.<String>emptyList(), this, toolkit);

        // take care of the VCF headers

        final Set<VCFHeaderLine> headerLines = VCFUtils.smartMergeHeaders(vcfRods.values(), true);

        headerLines.addAll(annotationEngine.getVCFAnnotationDescriptions());

        headerLines.addAll(genotypingEngine.getAppropriateVCFInfoHeaders());

        // add the pool values for each genotype

        VCFStandardHeaderLines.addStandardInfoLines(headerLines, true, VCFConstants.MLE_ALLELE_COUNT_KEY, VCFConstants.MLE_ALLELE_FREQUENCY_KEY);

        if ( dbsnp != null && dbsnp.dbsnp.isBound() )

            VCFStandardHeaderLines.addStandardInfoLines(headerLines, true, VCFConstants.DBSNP_KEY);

        final Set<String> sampleNameSet = SampleListUtils.asSet(samples);

        final VCFHeader vcfHeader = new VCFHeader(headerLines, sampleNameSet);

        vcfWriter.writeHeader(vcfHeader);

        logger.info("Notice that the -ploidy parameter is ignored in " + getClass().getSimpleName() + " tool as this is automatically determined by the input variant files");

    }

    public VariantContext map(final RefMetaDataTracker tracker, final ReferenceContext ref, final AlignmentContext context) {

        if ( tracker == null ) // RodWalkers can make funky map calls

            return null;

        final GenomeLoc loc = ref.getLocus();

        final VariantContext combinedVC = ReferenceConfidenceVariantContextMerger.merge(tracker.getPrioritizedValue(variants, loc), loc, INCLUDE_NON_VARIANTS ? ref.getBase() : null, true);

        if ( combinedVC == null )

            return null;

        return regenotypeVC(tracker, ref, combinedVC);

    }

    /**

     * Re-genotype (and re-annotate) a combined genomic VC

     *

     * @param tracker        the ref tracker

     * @param ref            the ref context

     * @param originalVC     the combined genomic VC

     * @return a new VariantContext or null if the site turned monomorphic and we don't want such sites

     */

    protected VariantContext regenotypeVC(final RefMetaDataTracker tracker, final ReferenceContext ref, final VariantContext originalVC) {

        if ( originalVC == null ) throw new IllegalArgumentException("originalVC cannot be null");

        VariantContext result = originalVC;

        // only re-genotype polymorphic sites

        if ( result.isVariant() ) {

            VariantContext regenotypedVC = genotypingEngine.calculateGenotypes(result);

            if ( regenotypedVC == null) {

                if (!INCLUDE_NON_VARIANTS)

                    return null;

            }

            else {

                regenotypedVC = GATKVariantContextUtils.reverseTrimAlleles(regenotypedVC);

                result = addGenotypingAnnotations(originalVC.getAttributes(), regenotypedVC);

            }

        }

        // if it turned monomorphic then we either need to ignore or fix such sites

        boolean createRefGTs = false;

        if ( result.isMonomorphicInSamples() ) {

            if ( !INCLUDE_NON_VARIANTS )

                return null;

            createRefGTs = true;

        }

        // Re-annotate and fix/remove some of the original annotations.

        // Note that the order of these actions matters and is different for polymorphic and monomorphic sites.

        // For polymorphic sites we need to make sure e.g. the SB tag is sent to the annotation engine and then removed later.

        // For monomorphic sites we need to make sure e.g. the hom ref genotypes are created and only then are passed to the annotation engine.

        // We could theoretically make 2 passes to re-create the genotypes, but that gets extremely expensive with large sample sizes.

        if ( createRefGTs ) {

            result = new VariantContextBuilder(result).genotypes(cleanupGenotypeAnnotations(result, true)).make();

            result = annotationEngine.annotateContext(tracker, ref, null, result);

        } else {

            result = annotationEngine.annotateContext(tracker, ref, null, result);

            result = new VariantContextBuilder(result).genotypes(cleanupGenotypeAnnotations(result, false)).make();

        }

        return result;

    }

    /**

     * Add genotyping-based annotations to the new VC

     *

     * @param originalAttributes the non-null annotations from the original VC

     * @param newVC the new non-null VC

     * @return a non-null VC

     */

    private VariantContext addGenotypingAnnotations(final Map<String, Object> originalAttributes, final VariantContext newVC) {

        // we want to carry forward the attributes from the original VC but make sure to add the MLE-based annotations

        final Map<String, Object> attrs = new HashMap<>(originalAttributes);

        attrs.put(VCFConstants.MLE_ALLELE_COUNT_KEY, newVC.getAttribute(VCFConstants.MLE_ALLELE_COUNT_KEY));

        attrs.put(VCFConstants.MLE_ALLELE_FREQUENCY_KEY, newVC.getAttribute(VCFConstants.MLE_ALLELE_FREQUENCY_KEY));

        if (newVC.hasAttribute(GenotypingEngine.NUMBER_OF_DISCOVERED_ALLELES_KEY))

            attrs.put(GenotypingEngine.NUMBER_OF_DISCOVERED_ALLELES_KEY, newVC.getAttribute(GenotypingEngine.NUMBER_OF_DISCOVERED_ALLELES_KEY));

        return new VariantContextBuilder(newVC).attributes(attrs).make();

    }

    /**

     * Cleans up genotype-level annotations that need to be updated.

     * 1. move MIN_DP to DP if present

     * 2. propagate DP to AD if not present

     * 3. remove SB if present

     * 4. change the PGT value from "0|1" to "1|1" for homozygous variant genotypes

     *

     * @param VC            the VariantContext with the Genotypes to fix

     * @param createRefGTs  if true we will also create proper hom ref genotypes since we assume the site is monomorphic

     * @return a new set of Genotypes

     */

    private List<Genotype> cleanupGenotypeAnnotations(final VariantContext VC, final boolean createRefGTs) {

        final GenotypesContext oldGTs = VC.getGenotypes();

        final List<Genotype> recoveredGs = new ArrayList<>(oldGTs.size());

        for ( final Genotype oldGT : oldGTs ) {

            final Map<String, Object> attrs = new HashMap<>(oldGT.getExtendedAttributes());

            final GenotypeBuilder builder = new GenotypeBuilder(oldGT);

            int depth = oldGT.hasDP() ? oldGT.getDP() : 0;

            // move the MIN_DP to DP

            if ( oldGT.hasExtendedAttribute("MIN_DP") ) {

                depth = Integer.parseInt((String)oldGT.getAnyAttribute("MIN_DP"));

                builder.DP(depth);

                attrs.remove("MIN_DP");

            }

            // remove SB

            attrs.remove("SB");

            // update PGT for hom vars

            if ( oldGT.isHomVar() && oldGT.hasExtendedAttribute(HaplotypeCaller.HAPLOTYPE_CALLER_PHASING_GT_KEY) ) {

                attrs.put(HaplotypeCaller.HAPLOTYPE_CALLER_PHASING_GT_KEY, "1|1");

            }

            // create AD if it's not there

            if ( !oldGT.hasAD() && VC.isVariant() ) {

                final int[] AD = new int[VC.getNAlleles()];

                AD[0] = depth;

                builder.AD(AD);

            }

            if ( createRefGTs ) {

                final int ploidy = oldGT.getPloidy();

                final List<Allele> refAlleles = Collections.nCopies(ploidy,VC.getReference());

                //keep 0 depth samples as no-call

                if (depth > 0) {

                    builder.alleles(refAlleles);

                }

                // also, the PLs are technically no longer usable

                builder.noPL();

            }

            recoveredGs.add(builder.noAttributes().attributes(attrs).make());

        }

        return recoveredGs;

    }

    /**

     * Creates a UnifiedArgumentCollection with appropriate values filled in from the arguments in this walker

     * @return a complete UnifiedArgumentCollection

     */

    private UnifiedArgumentCollection createUAC() {

        UnifiedArgumentCollection uac = new UnifiedArgumentCollection();

        uac.genotypeArgs = genotypeArgs.clone();

        return uac;

    }

    public VariantContextWriter reduceInit() {

        return vcfWriter;

    }

    public VariantContextWriter reduce(final VariantContext vc, final VariantContextWriter writer) {

        if ( vc != null )

            writer.add(vc);

        return writer;

    }

    @Override

    public VariantContextWriter treeReduce(final VariantContextWriter lhs, final VariantContextWriter rhs) {

        return lhs;

    }

    @Override

    public void onTraversalDone(final VariantContextWriter writer) {}

}