/**
   * Takes the interval, finds it in the stash, prints it to the VCF
   *
   * @param stats The statistics of the interval
   * @param refAllele the reference allele
   */
  private void outputStatsToVCF(final IntervalStratification stats, final Allele refAllele) {
    GenomeLoc interval = stats.getInterval();

    final List<Allele> alleles = new ArrayList<>();
    final Map<String, Object> attributes = new HashMap<>();
    final ArrayList<Genotype> genotypes = new ArrayList<>();

    for (String sample : samples) {
      final GenotypeBuilder gb = new GenotypeBuilder(sample);

      SampleStratification sampleStat = stats.getSampleStatistics(sample);
      gb.attribute(
          GATKVCFConstants.AVG_INTERVAL_DP_BY_SAMPLE_KEY,
          sampleStat.averageCoverage(interval.size()));
      gb.attribute(GATKVCFConstants.LOW_COVERAGE_LOCI, sampleStat.getNLowCoveredLoci());
      gb.attribute(GATKVCFConstants.ZERO_COVERAGE_LOCI, sampleStat.getNUncoveredLoci());
      gb.filters(statusToStrings(stats.getSampleStatistics(sample).callableStatuses(), false));

      genotypes.add(gb.make());
    }
    alleles.add(refAllele);
    alleles.add(SYMBOLIC_ALLELE);
    VariantContextBuilder vcb =
        new VariantContextBuilder(
            "DiagnoseTargets",
            interval.getContig(),
            interval.getStart(),
            interval.getStop(),
            alleles);

    vcb = vcb.log10PError(VariantContext.NO_LOG10_PERROR);
    vcb.filters(new LinkedHashSet<>(statusToStrings(stats.callableStatuses(), true)));

    attributes.put(VCFConstants.END_KEY, interval.getStop());
    attributes.put(GATKVCFConstants.AVG_INTERVAL_DP_KEY, stats.averageCoverage(interval.size()));
    attributes.put(GATKVCFConstants.INTERVAL_GC_CONTENT_KEY, stats.gcContent());

    vcb = vcb.attributes(attributes);
    vcb = vcb.genotypes(genotypes);

    vcfWriter.add(vcb.make());
  }
  /**
   * Merges VariantContexts into a single hybrid. Takes genotypes for common samples in priority
   * order, if provided. If uniqifySamples is true, the priority order is ignored and names are
   * created by concatenating the VC name with the sample name
   *
   * @param genomeLocParser loc parser
   * @param unsortedVCs collection of unsorted VCs
   * @param priorityListOfVCs priority list detailing the order in which we should grab the VCs
   * @param filteredRecordMergeType merge type for filtered records
   * @param genotypeMergeOptions merge option for genotypes
   * @param annotateOrigin should we annotate the set it came from?
   * @param printMessages should we print messages?
   * @param setKey the key name of the set
   * @param filteredAreUncalled are filtered records uncalled?
   * @param mergeInfoWithMaxAC should we merge in info from the VC with maximum allele count?
   * @return new VariantContext representing the merge of unsortedVCs
   */
  public static VariantContext simpleMerge(
      final GenomeLocParser genomeLocParser,
      final Collection<VariantContext> unsortedVCs,
      final List<String> priorityListOfVCs,
      final FilteredRecordMergeType filteredRecordMergeType,
      final GenotypeMergeType genotypeMergeOptions,
      final boolean annotateOrigin,
      final boolean printMessages,
      final String setKey,
      final boolean filteredAreUncalled,
      final boolean mergeInfoWithMaxAC) {
    if (unsortedVCs == null || unsortedVCs.size() == 0) return null;

    if (annotateOrigin && priorityListOfVCs == null)
      throw new IllegalArgumentException(
          "Cannot merge calls and annotate their origins without a complete priority list of VariantContexts");

    if (genotypeMergeOptions == GenotypeMergeType.REQUIRE_UNIQUE)
      verifyUniqueSampleNames(unsortedVCs);

    List<VariantContext> prepaddedVCs =
        sortVariantContextsByPriority(unsortedVCs, priorityListOfVCs, genotypeMergeOptions);
    // Make sure all variant contexts are padded with reference base in case of indels if necessary
    List<VariantContext> VCs = new ArrayList<VariantContext>();

    for (VariantContext vc : prepaddedVCs) {
      // also a reasonable place to remove filtered calls, if needed
      if (!filteredAreUncalled || vc.isNotFiltered())
        VCs.add(createVariantContextWithPaddedAlleles(vc, false));
    }
    if (VCs.size() == 0) // everything is filtered out and we're filteredAreUncalled
    return null;

    // establish the baseline info from the first VC
    final VariantContext first = VCs.get(0);
    final String name = first.getSource();
    final Allele refAllele = determineReferenceAllele(VCs);

    final Set<Allele> alleles = new LinkedHashSet<Allele>();
    final Set<String> filters = new TreeSet<String>();
    final Map<String, Object> attributes = new TreeMap<String, Object>();
    final Set<String> inconsistentAttributes = new HashSet<String>();
    final Set<String> variantSources =
        new HashSet<
            String>(); // contains the set of sources we found in our set of VCs that are variant
    final Set<String> rsIDs = new LinkedHashSet<String>(1); // most of the time there's one id

    GenomeLoc loc = getLocation(genomeLocParser, first);
    int depth = 0;
    int maxAC = -1;
    final Map<String, Object> attributesWithMaxAC = new TreeMap<String, Object>();
    double log10PError = 1;
    VariantContext vcWithMaxAC = null;
    GenotypesContext genotypes = GenotypesContext.create();

    // counting the number of filtered and variant VCs
    int nFiltered = 0;

    boolean remapped = false;

    // cycle through and add info from the other VCs, making sure the loc/reference matches

    for (VariantContext vc : VCs) {
      if (loc.getStart() != vc.getStart()) // || !first.getReference().equals(vc.getReference()) )
      throw new ReviewedStingException(
            "BUG: attempting to merge VariantContexts with different start sites: first="
                + first.toString()
                + " second="
                + vc.toString());

      if (getLocation(genomeLocParser, vc).size() > loc.size())
        loc = getLocation(genomeLocParser, vc); // get the longest location

      nFiltered += vc.isFiltered() ? 1 : 0;
      if (vc.isVariant()) variantSources.add(vc.getSource());

      AlleleMapper alleleMapping = resolveIncompatibleAlleles(refAllele, vc, alleles);
      remapped = remapped || alleleMapping.needsRemapping();

      alleles.addAll(alleleMapping.values());

      mergeGenotypes(
          genotypes, vc, alleleMapping, genotypeMergeOptions == GenotypeMergeType.UNIQUIFY);

      log10PError = Math.min(log10PError, vc.isVariant() ? vc.getLog10PError() : 1);

      filters.addAll(vc.getFilters());

      //
      // add attributes
      //
      // special case DP (add it up) and ID (just preserve it)
      //
      if (vc.hasAttribute(VCFConstants.DEPTH_KEY))
        depth += vc.getAttributeAsInt(VCFConstants.DEPTH_KEY, 0);
      if (vc.hasID()) rsIDs.add(vc.getID());
      if (mergeInfoWithMaxAC && vc.hasAttribute(VCFConstants.ALLELE_COUNT_KEY)) {
        String rawAlleleCounts = vc.getAttributeAsString(VCFConstants.ALLELE_COUNT_KEY, null);
        // lets see if the string contains a , separator
        if (rawAlleleCounts.contains(VCFConstants.INFO_FIELD_ARRAY_SEPARATOR)) {
          List<String> alleleCountArray =
              Arrays.asList(
                  rawAlleleCounts
                      .substring(1, rawAlleleCounts.length() - 1)
                      .split(VCFConstants.INFO_FIELD_ARRAY_SEPARATOR));
          for (String alleleCount : alleleCountArray) {
            final int ac = Integer.valueOf(alleleCount.trim());
            if (ac > maxAC) {
              maxAC = ac;
              vcWithMaxAC = vc;
            }
          }
        } else {
          final int ac = Integer.valueOf(rawAlleleCounts);
          if (ac > maxAC) {
            maxAC = ac;
            vcWithMaxAC = vc;
          }
        }
      }

      for (Map.Entry<String, Object> p : vc.getAttributes().entrySet()) {
        String key = p.getKey();
        // if we don't like the key already, don't go anywhere
        if (!inconsistentAttributes.contains(key)) {
          boolean alreadyFound = attributes.containsKey(key);
          Object boundValue = attributes.get(key);
          boolean boundIsMissingValue =
              alreadyFound && boundValue.equals(VCFConstants.MISSING_VALUE_v4);

          if (alreadyFound && !boundValue.equals(p.getValue()) && !boundIsMissingValue) {
            // we found the value but we're inconsistent, put it in the exclude list
            // System.out.printf("Inconsistent INFO values: %s => %s and %s%n", key, boundValue,
            // p.getValue());
            inconsistentAttributes.add(key);
            attributes.remove(key);
          } else if (!alreadyFound || boundIsMissingValue) { // no value
            // if ( vc != first ) System.out.printf("Adding key %s => %s%n", p.getKey(),
            // p.getValue());
            attributes.put(key, p.getValue());
          }
        }
      }
    }

    // if we have more alternate alleles in the merged VC than in one or more of the
    // original VCs, we need to strip out the GL/PLs (because they are no longer accurate), as well
    // as allele-dependent attributes like AC,AF
    for (VariantContext vc : VCs) {
      if (vc.alleles.size() == 1) continue;
      if (hasPLIncompatibleAlleles(alleles, vc.alleles)) {
        if (!genotypes.isEmpty())
          logger.warn(
              String.format(
                  "Stripping PLs at %s due incompatible alleles merged=%s vs. single=%s",
                  genomeLocParser.createGenomeLoc(vc), alleles, vc.alleles));
        genotypes = stripPLs(genotypes);
        // this will remove stale AC,AF attributed from vc
        calculateChromosomeCounts(vc, attributes, true);
        break;
      }
    }

    // take the VC with the maxAC and pull the attributes into a modifiable map
    if (mergeInfoWithMaxAC && vcWithMaxAC != null) {
      attributesWithMaxAC.putAll(vcWithMaxAC.getAttributes());
    }

    // if at least one record was unfiltered and we want a union, clear all of the filters
    if ((filteredRecordMergeType == FilteredRecordMergeType.KEEP_IF_ANY_UNFILTERED
            && nFiltered != VCs.size())
        || filteredRecordMergeType == FilteredRecordMergeType.KEEP_UNCONDITIONAL) filters.clear();

    if (annotateOrigin) { // we care about where the call came from
      String setValue;
      if (nFiltered == 0
          && variantSources.size() == priorityListOfVCs.size()) // nothing was unfiltered
      setValue = MERGE_INTERSECTION;
      else if (nFiltered == VCs.size()) // everything was filtered out
      setValue = MERGE_FILTER_IN_ALL;
      else if (variantSources.isEmpty()) // everyone was reference
      setValue = MERGE_REF_IN_ALL;
      else {
        LinkedHashSet<String> s = new LinkedHashSet<String>();
        for (VariantContext vc : VCs)
          if (vc.isVariant())
            s.add(vc.isFiltered() ? MERGE_FILTER_PREFIX + vc.getSource() : vc.getSource());
        setValue = Utils.join("-", s);
      }

      if (setKey != null) {
        attributes.put(setKey, setValue);
        if (mergeInfoWithMaxAC && vcWithMaxAC != null) {
          attributesWithMaxAC.put(setKey, vcWithMaxAC.getSource());
        }
      }
    }

    if (depth > 0) attributes.put(VCFConstants.DEPTH_KEY, String.valueOf(depth));

    final String ID = rsIDs.isEmpty() ? VCFConstants.EMPTY_ID_FIELD : Utils.join(",", rsIDs);

    final VariantContextBuilder builder = new VariantContextBuilder().source(name).id(ID);
    builder.loc(loc.getContig(), loc.getStart(), loc.getStop());
    builder.alleles(alleles);
    builder.genotypes(genotypes);
    builder.log10PError(log10PError);
    builder.filters(filters).attributes(mergeInfoWithMaxAC ? attributesWithMaxAC : attributes);

    // Trim the padded bases of all alleles if necessary
    VariantContext merged = createVariantContextWithTrimmedAlleles(builder.make());
    if (printMessages && remapped) System.out.printf("Remapped => %s%n", merged);
    return merged;
  }
  /**
   * Main entry function to calculate genotypes of a given VC with corresponding GL's
   *
   * @param tracker Tracker
   * @param refContext Reference context
   * @param rawContext Raw context
   * @param stratifiedContexts Stratified alignment contexts
   * @param vc Input VC
   * @param model GL calculation model
   * @param inheritAttributesFromInputVC Output VC will contain attributes inherited from input vc
   * @return VC with assigned genotypes
   */
  public VariantCallContext calculateGenotypes(
      final RefMetaDataTracker tracker,
      final ReferenceContext refContext,
      final AlignmentContext rawContext,
      Map<String, AlignmentContext> stratifiedContexts,
      final VariantContext vc,
      final GenotypeLikelihoodsCalculationModel.Model model,
      final boolean inheritAttributesFromInputVC,
      final Map<String, org.broadinstitute.sting.utils.genotyper.PerReadAlleleLikelihoodMap>
          perReadAlleleLikelihoodMap) {

    boolean limitedContext =
        tracker == null || refContext == null || rawContext == null || stratifiedContexts == null;

    // initialize the data for this thread if that hasn't been done yet
    if (afcm.get() == null) {
      afcm.set(AFCalcFactory.createAFCalc(UAC, N, logger));
    }

    // estimate our confidence in a reference call and return
    if (vc.getNSamples() == 0) {
      if (limitedContext) return null;
      return (UAC.OutputMode != OUTPUT_MODE.EMIT_ALL_SITES
          ? estimateReferenceConfidence(vc, stratifiedContexts, getTheta(model), false, 1.0)
          : generateEmptyContext(tracker, refContext, stratifiedContexts, rawContext));
    }

    AFCalcResult AFresult = afcm.get().getLog10PNonRef(vc, getAlleleFrequencyPriors(model));

    // is the most likely frequency conformation AC=0 for all alternate alleles?
    boolean bestGuessIsRef = true;

    // determine which alternate alleles have AF>0
    final List<Allele> myAlleles = new ArrayList<Allele>(vc.getAlleles().size());
    final List<Integer> alleleCountsofMLE = new ArrayList<Integer>(vc.getAlleles().size());
    myAlleles.add(vc.getReference());
    for (int i = 0; i < AFresult.getAllelesUsedInGenotyping().size(); i++) {
      final Allele alternateAllele = AFresult.getAllelesUsedInGenotyping().get(i);
      if (alternateAllele.isReference()) continue;

      // we are non-ref if the probability of being non-ref > the emit confidence.
      // the emit confidence is phred-scaled, say 30 => 10^-3.
      // the posterior AF > 0 is log10: -5 => 10^-5
      // we are non-ref if 10^-5 < 10^-3 => -5 < -3
      final boolean isNonRef =
          AFresult.isPolymorphic(alternateAllele, UAC.STANDARD_CONFIDENCE_FOR_EMITTING / -10.0);

      // if the most likely AC is not 0, then this is a good alternate allele to use
      if (isNonRef) {
        myAlleles.add(alternateAllele);
        alleleCountsofMLE.add(AFresult.getAlleleCountAtMLE(alternateAllele));
        bestGuessIsRef = false;
      }
      // if in GENOTYPE_GIVEN_ALLELES mode, we still want to allow the use of a poor allele
      else if (UAC.GenotypingMode
          == GenotypeLikelihoodsCalculationModel.GENOTYPING_MODE.GENOTYPE_GIVEN_ALLELES) {
        myAlleles.add(alternateAllele);
        alleleCountsofMLE.add(AFresult.getAlleleCountAtMLE(alternateAllele));
      }
    }

    final double PoFGT0 = Math.pow(10, AFresult.getLog10PosteriorOfAFGT0());

    // note the math.abs is necessary because -10 * 0.0 => -0.0 which isn't nice
    final double phredScaledConfidence =
        Math.abs(
            !bestGuessIsRef
                    || UAC.GenotypingMode
                        == GenotypeLikelihoodsCalculationModel.GENOTYPING_MODE
                            .GENOTYPE_GIVEN_ALLELES
                ? -10 * AFresult.getLog10PosteriorOfAFEq0()
                : -10 * AFresult.getLog10PosteriorOfAFGT0());

    // return a null call if we don't pass the confidence cutoff or the most likely allele frequency
    // is zero
    if (UAC.OutputMode != OUTPUT_MODE.EMIT_ALL_SITES
        && !passesEmitThreshold(phredScaledConfidence, bestGuessIsRef)) {
      // technically, at this point our confidence in a reference call isn't accurately estimated
      //  because it didn't take into account samples with no data, so let's get a better estimate
      return limitedContext
          ? null
          : estimateReferenceConfidence(vc, stratifiedContexts, getTheta(model), true, PoFGT0);
    }

    // start constructing the resulting VC
    final GenomeLoc loc = genomeLocParser.createGenomeLoc(vc);
    final VariantContextBuilder builder =
        new VariantContextBuilder(
            "UG_call", loc.getContig(), loc.getStart(), loc.getStop(), myAlleles);
    builder.log10PError(phredScaledConfidence / -10.0);
    if (!passesCallThreshold(phredScaledConfidence)) builder.filters(filter);

    // create the genotypes
    final GenotypesContext genotypes = afcm.get().subsetAlleles(vc, myAlleles, true, ploidy);
    builder.genotypes(genotypes);

    // print out stats if we have a writer
    if (verboseWriter != null && !limitedContext)
      printVerboseData(refContext.getLocus().toString(), vc, PoFGT0, phredScaledConfidence, model);

    // *** note that calculating strand bias involves overwriting data structures, so we do that
    // last
    final HashMap<String, Object> attributes = new HashMap<String, Object>();

    // inherit attributed from input vc if requested
    if (inheritAttributesFromInputVC) attributes.putAll(vc.getAttributes());
    // if the site was downsampled, record that fact
    if (!limitedContext && rawContext.hasPileupBeenDownsampled())
      attributes.put(VCFConstants.DOWNSAMPLED_KEY, true);

    if (UAC.ANNOTATE_NUMBER_OF_ALLELES_DISCOVERED)
      attributes.put(NUMBER_OF_DISCOVERED_ALLELES_KEY, vc.getAlternateAlleles().size());

    // add the MLE AC and AF annotations
    if (alleleCountsofMLE.size() > 0) {
      attributes.put(VCFConstants.MLE_ALLELE_COUNT_KEY, alleleCountsofMLE);
      final int AN = builder.make().getCalledChrCount();
      final ArrayList<Double> MLEfrequencies = new ArrayList<Double>(alleleCountsofMLE.size());
      // the MLEAC is allowed to be larger than the AN (e.g. in the case of all PLs being 0, the GT
      // is ./. but the exact model may arbitrarily choose an AC>1)
      for (int AC : alleleCountsofMLE) MLEfrequencies.add(Math.min(1.0, (double) AC / (double) AN));
      attributes.put(VCFConstants.MLE_ALLELE_FREQUENCY_KEY, MLEfrequencies);
    }

    if (UAC.COMPUTE_SLOD && !limitedContext && !bestGuessIsRef) {
      // final boolean DEBUG_SLOD = false;

      // the overall lod
      // double overallLog10PofNull = AFresult.log10AlleleFrequencyPosteriors[0];
      double overallLog10PofF = AFresult.getLog10LikelihoodOfAFGT0();
      // if ( DEBUG_SLOD ) System.out.println("overallLog10PofF=" + overallLog10PofF);

      List<Allele> allAllelesToUse = builder.make().getAlleles();

      // the forward lod
      VariantContext vcForward =
          calculateLikelihoods(
              tracker,
              refContext,
              stratifiedContexts,
              AlignmentContextUtils.ReadOrientation.FORWARD,
              allAllelesToUse,
              false,
              model,
              perReadAlleleLikelihoodMap);
      AFresult = afcm.get().getLog10PNonRef(vcForward, getAlleleFrequencyPriors(model));
      // double[] normalizedLog10Posteriors =
      // MathUtils.normalizeFromLog10(AFresult.log10AlleleFrequencyPosteriors, true);
      double forwardLog10PofNull = AFresult.getLog10LikelihoodOfAFEq0();
      double forwardLog10PofF = AFresult.getLog10LikelihoodOfAFGT0();
      // if ( DEBUG_SLOD ) System.out.println("forwardLog10PofNull=" + forwardLog10PofNull + ",
      // forwardLog10PofF=" + forwardLog10PofF);

      // the reverse lod
      VariantContext vcReverse =
          calculateLikelihoods(
              tracker,
              refContext,
              stratifiedContexts,
              AlignmentContextUtils.ReadOrientation.REVERSE,
              allAllelesToUse,
              false,
              model,
              perReadAlleleLikelihoodMap);
      AFresult = afcm.get().getLog10PNonRef(vcReverse, getAlleleFrequencyPriors(model));
      // normalizedLog10Posteriors =
      // MathUtils.normalizeFromLog10(AFresult.log10AlleleFrequencyPosteriors, true);
      double reverseLog10PofNull = AFresult.getLog10LikelihoodOfAFEq0();
      double reverseLog10PofF = AFresult.getLog10LikelihoodOfAFGT0();
      // if ( DEBUG_SLOD ) System.out.println("reverseLog10PofNull=" + reverseLog10PofNull + ",
      // reverseLog10PofF=" + reverseLog10PofF);

      double forwardLod = forwardLog10PofF + reverseLog10PofNull - overallLog10PofF;
      double reverseLod = reverseLog10PofF + forwardLog10PofNull - overallLog10PofF;
      // if ( DEBUG_SLOD ) System.out.println("forward lod=" + forwardLod + ", reverse lod=" +
      // reverseLod);

      // strand score is max bias between forward and reverse strands
      double strandScore = Math.max(forwardLod, reverseLod);
      // rescale by a factor of 10
      strandScore *= 10.0;
      // logger.debug(String.format("SLOD=%f", strandScore));

      if (!Double.isNaN(strandScore)) attributes.put("SB", strandScore);
    }

    // finish constructing the resulting VC
    builder.attributes(attributes);
    VariantContext vcCall = builder.make();

    // if we are subsetting alleles (either because there were too many or because some were not
    // polymorphic)
    // then we may need to trim the alleles (because the original VariantContext may have had to pad
    // at the end).
    if (myAlleles.size() != vc.getAlleles().size()
        && !limitedContext) // limitedContext callers need to handle allele trimming on their own to
                            // keep their perReadAlleleLikelihoodMap alleles in sync
    vcCall = VariantContextUtils.reverseTrimAlleles(vcCall);

    if (annotationEngine != null
        && !limitedContext) { // limitedContext callers need to handle annotations on their own by
                              // calling their own annotationEngine
      // Note: we want to use the *unfiltered* and *unBAQed* context for the annotations
      final ReadBackedPileup pileup = rawContext.getBasePileup();
      stratifiedContexts = AlignmentContextUtils.splitContextBySampleName(pileup);

      vcCall =
          annotationEngine.annotateContext(
              tracker, refContext, stratifiedContexts, vcCall, perReadAlleleLikelihoodMap);
    }

    return new VariantCallContext(vcCall, confidentlyCalled(phredScaledConfidence, PoFGT0));
  }