Examples with GenotypeBuilder htsjdk.variant.variantcontext.GenotypeBuilder used on opensource projects

Example 36 with GenotypeBuilder

use of htsjdk.variant.variantcontext.GenotypeBuilder in project jvarkit by lindenb.

the class VcfGroupByPopulation method doVcfToVcf.

@Override
protected int doVcfToVcf(String inputName, VcfIterator vcfIn, VariantContextWriter out) {
    try {
        Reader r = IOUtils.openFileForBufferedReading(this.mappingFile);
        parsePopulationMapping(r);
        r.close();
        VCFHeader header = vcfIn.getHeader();
        Set<String> samplesInVcf = new HashSet<>(header.getSampleNamesInOrder());
        this.sample2population.keySet().retainAll(samplesInVcf);
        Map<String, Set<String>> population2samples = new HashMap<>();
        for (String sample : this.sample2population.keySet()) {
            String pop = this.sample2population.get(sample);
            Set<String> samples = population2samples.get(pop);
            if (samples == null) {
                samples = new HashSet<>();
                population2samples.put(pop, samples);
            }
            samples.add(sample);
        }
        for (String sample : header.getSampleNamesInOrder()) {
            if (!this.sample2population.containsKey(sample)) {
                throw new IOException("Sample " + sample + " not affected to a population");
            }
        }
        Set<VCFHeaderLine> metaData = new LinkedHashSet<>();
        for (VCFHeaderLine vhl : header.getMetaDataInInputOrder()) {
            if (!(vhl instanceof VCFContigHeaderLine))
                continue;
            metaData.add(vhl);
        }
        metaData.add(new VCFHeaderLine(getClass().getSimpleName() + "CmdLine", String.valueOf(getProgramCommandLine())));
        metaData.add(new VCFHeaderLine(getClass().getSimpleName() + "Version", String.valueOf(getVersion())));
        metaData.add(new VCFHeaderLine(getClass().getSimpleName() + "HtsJdkVersion", HtsjdkVersion.getVersion()));
        metaData.add(new VCFHeaderLine(getClass().getSimpleName() + "HtsJdkHome", HtsjdkVersion.getHome()));
        /* FORMAT */
        metaData.add(new VCFFormatHeaderLine("NS", 1, VCFHeaderLineType.Integer, "Total Number of Samples"));
        metaData.add(new VCFFormatHeaderLine("R", 1, VCFHeaderLineType.Integer, "Number of alleles REF (hom:=2,het:=1)"));
        metaData.add(new VCFFormatHeaderLine("A", 1, VCFHeaderLineType.Integer, "Number of alleles ALT (hom:=2,het:=1)"));
        metaData.add(new VCFFormatHeaderLine("UNC", 1, VCFHeaderLineType.Integer, "Number of NON-called samples"));
        metaData.add(new VCFFormatHeaderLine("F", 1, VCFHeaderLineType.Float, "Allele Frequency A/(R+A)"));
        metaData.add(new VCFFormatHeaderLine("DP", 1, VCFHeaderLineType.Integer, "Depth"));
        /* INFO */
        metaData.add(new VCFInfoHeaderLine("NS", 1, VCFHeaderLineType.Integer, "Total Number of Samples"));
        metaData.add(new VCFInfoHeaderLine("R", 1, VCFHeaderLineType.Integer, "Number of alleles REF (hom:=2,het:=1)"));
        metaData.add(new VCFInfoHeaderLine("A", 1, VCFHeaderLineType.Integer, "Number of alleles ALT (hom:=2,het:=1)"));
        metaData.add(new VCFInfoHeaderLine("UNC", 1, VCFHeaderLineType.Integer, "Number of NON-called samples"));
        metaData.add(new VCFInfoHeaderLine("F", 1, VCFHeaderLineType.Float, "Allele Frequency A/(R+A)"));
        metaData.add(new VCFInfoHeaderLine("DP", 1, VCFHeaderLineType.Integer, "Depth"));
        metaData.add(new VCFFormatHeaderLine("GT", 1, VCFHeaderLineType.String, "Genotype"));
        VCFHeader h2 = new VCFHeader(metaData, population2samples.keySet());
        out.writeHeader(h2);
        SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(vcfIn.getHeader());
        while (vcfIn.hasNext()) {
            VariantContext ctx = progress.watch(vcfIn.next());
            VariantContextBuilder vcb = new VariantContextBuilder(ctx.getSource(), ctx.getContig(), ctx.getStart(), ctx.getEnd(), ctx.getAlleles());
            if (ctx.hasID())
                vcb.id(ctx.getID());
            GCount count_ctx = new GCount();
            List<Genotype> genotypes = new ArrayList<>(population2samples.size());
            for (String pop : population2samples.keySet()) {
                GCount count = new GCount();
                Set<String> samples = population2samples.get(pop);
                for (String sample : samples) {
                    Genotype g = ctx.getGenotype(sample);
                    count.watch(g);
                }
                GenotypeBuilder gb = new GenotypeBuilder(pop);
                gb.attribute("NS", samples.size());
                gb.attribute("R", count.R);
                gb.attribute("A", count.A);
                gb.attribute("UNC", count.uncalled);
                if (count.R + count.A > 0) {
                    gb.attribute("F", (float) count.A / (float) (count.R + count.A));
                }
                if (count.dp >= 0) {
                    gb.attribute("DP", count.dp);
                    if (count_ctx.dp == -1)
                        count_ctx.dp = 0;
                }
                genotypes.add(gb.make());
                count_ctx.R += count.R;
                count_ctx.A += count.A;
                count_ctx.uncalled += count.uncalled;
                count_ctx.dp += count.dp;
            }
            vcb.attribute("R", count_ctx.R);
            vcb.attribute("A", count_ctx.A);
            vcb.attribute("UNC", count_ctx.uncalled);
            if (count_ctx.R + count_ctx.A > 0) {
                vcb.attribute("F", (float) count_ctx.A / (float) (count_ctx.R + count_ctx.A));
            }
            if (count_ctx.dp >= 0) {
                vcb.attribute("DP", count_ctx.dp);
            }
            vcb.attribute("NS", this.sample2population.keySet().size());
            vcb.genotypes(genotypes);
            out.add(vcb.make());
        }
        progress.finish();
        return 0;
    } catch (Exception err) {
        LOG.error(err);
        return -1;
    }
}

Example 37 with GenotypeBuilder

use of htsjdk.variant.variantcontext.GenotypeBuilder in project jvarkit by lindenb.

the class MsaToVcf method doWork.

@Override
public int doWork(final List<String> args) {
    VariantContextWriter w = null;
    LineIterator r = null;
    try {
        final String inputName = oneFileOrNull(args);
        if (inputName == null) {
            LOG.info("Reading from stdin");
            r = IOUtils.openStreamForLineIterator(stdin());
        } else {
            LOG.info("Reading from " + inputName);
            r = IOUtils.openURIForLineIterator(inputName);
        }
        Format format = Format.None;
        /**
         * try to guess format
         */
        while (r.hasNext() && format == Format.None) {
            final String line = r.peek();
            if (line.trim().isEmpty()) {
                r.next();
                continue;
            }
            if (line.startsWith("CLUSTAL")) {
                format = Format.Clustal;
                // consume
                r.next();
                break;
            } else if (line.startsWith(">")) {
                format = Format.Fasta;
                break;
            } else {
                LOG.error("MSA format not recognized in " + line);
                return -1;
            }
        }
        LOG.info("format : " + format);
        /**
         * parse lines as FASTA
         */
        if (Format.Fasta.equals(format)) {
            this.consensus = new FastaConsensus();
            AlignSequence curr = null;
            while (r.hasNext()) {
                String line = r.next();
                if (line.startsWith(">")) {
                    curr = new AlignSequence();
                    curr.name = line.substring(1).trim();
                    if (sample2sequence.containsKey(curr.name)) {
                        LOG.error("Sequence ID " + curr.name + " defined twice");
                        return -1;
                    }
                    sample2sequence.put(curr.name, curr);
                } else if (curr != null) {
                    curr.seq.append(line.trim());
                    this.align_length = Math.max(this.align_length, curr.seq.length());
                }
            }
        /*
				//remove heading & trailing '-'
				for(final String sample:this.sample2sequence.keySet())
					{
					final AlignSequence seq = this.sample2sequence.get(sample);
					int i=0;
					while(i<this.align_length && seq.at(i)==DELETION)
						{
						seq.seq.setCharAt(i, CLIPPING);
						++i;
						}
					i= this.align_length-1;
					while(i>=0 && seq.at(i)==DELETION)
						{
						seq.seq.setCharAt(i, CLIPPING);
						--i;
						}
					}*/
        } else /**
         * parse lines as CLUSTAL
         */
        if (Format.Clustal.equals(format)) {
            ClustalConsensus clustalconsensus = new ClustalConsensus();
            this.consensus = clustalconsensus;
            AlignSequence curr = null;
            int columnStart = -1;
            while (r.hasNext()) {
                String line = r.next();
                if (line.trim().isEmpty() || line.startsWith("CLUSTAL W")) {
                    columnStart = -1;
                    continue;
                }
                if (line.charAt(0) == ' ') {
                    if (columnStart == -1) {
                        LOG.error("illegal consensus line for " + line);
                        return -1;
                    }
                    /* if consensus doesn't exist in the first rows */
                    while (clustalconsensus.seq.length() < (this.align_length - (line.length() - columnStart))) {
                        clustalconsensus.seq.append(" ");
                    }
                    clustalconsensus.seq.append(line.substring(columnStart));
                } else {
                    if (columnStart == -1) {
                        columnStart = line.indexOf(' ');
                        if (columnStart == -1) {
                            LOG.error("no whithespace in " + line);
                            return -1;
                        }
                        while (columnStart < line.length() && line.charAt(columnStart) == ' ') {
                            columnStart++;
                        }
                    }
                    String seqname = line.substring(0, columnStart).trim();
                    curr = this.sample2sequence.get(seqname);
                    if (curr == null) {
                        curr = new AlignSequence();
                        curr.name = seqname;
                        this.sample2sequence.put(curr.name, curr);
                    }
                    int columnEnd = line.length();
                    // remove blanks and digit at the end
                    while (columnEnd - 1 > columnStart && (line.charAt(columnEnd - 1) == ' ' || Character.isDigit(line.charAt(columnEnd - 1)))) {
                        columnEnd--;
                    }
                    curr.seq.append(line.substring(columnStart, columnEnd));
                    this.align_length = Math.max(align_length, curr.seq.length());
                }
            }
        } else {
            LOG.error("Undefined input format");
            return -1;
        }
        CloserUtil.close(r);
        /* sequence consensus was set*/
        if (consensusRefName != null) {
            AlignSequence namedSequence = null;
            if ((namedSequence = sample2sequence.get(consensusRefName)) == null) {
                LOG.error("Cannot find consensus sequence \"" + consensusRefName + "\" in list of sequences: " + this.sample2sequence.keySet().toString());
                return -1;
            }
            this.consensus = new NamedConsensus(namedSequence);
        }
        /**
         * we're done, print VCF
         */
        /**
         * first, print header
         */
        Set<VCFHeaderLine> vcfHeaderLines = new HashSet<VCFHeaderLine>();
        vcfHeaderLines.add(new VCFInfoHeaderLine(VCFConstants.DEPTH_KEY, 1, VCFHeaderLineType.Integer, "Approximate read depth."));
        vcfHeaderLines.add(new VCFFormatHeaderLine(VCFConstants.GENOTYPE_KEY, 1, VCFHeaderLineType.String, "Genotype"));
        vcfHeaderLines.add(new VCFFormatHeaderLine(VCFConstants.DEPTH_KEY, 1, VCFHeaderLineType.Integer, "Approximate read depth"));
        // super.addMetaData(vcfHeaderLines);
        Map<String, String> mapping = new HashMap<String, String>();
        mapping.put("ID", REF);
        mapping.put("length", String.valueOf(this.align_length));
        vcfHeaderLines.add(new VCFContigHeaderLine(mapping, 1));
        Set<String> samples = new TreeSet<String>(this.sample2sequence.keySet());
        VCFHeader vcfHeader = new VCFHeader(vcfHeaderLines, samples);
        w = super.openVariantContextWriter(this.outputFile);
        w.writeHeader(vcfHeader);
        /**
         * loop over data, print header
         */
        int pos1 = 0;
        while (pos1 < align_length) {
            // is it a real variation or print all sites
            boolean is_variation;
            if (consensus.at(pos1) == MATCH) {
                if (this.printAllSites) {
                    is_variation = false;
                } else {
                    ++pos1;
                    continue;
                }
            } else {
                is_variation = true;
            }
            int pos2 = pos1 + 1;
            // don't extend if no variation and printAllSites
            while (is_variation && pos2 < align_length && consensus.at(pos2) != MATCH) {
                ++pos2;
            }
            boolean is_subsitution = (pos1 + 1 == pos2);
            if (// need pos1>0 because ALT contains prev base.
            is_subsitution && pos1 != 0 && is_variation) {
                for (Sequence seq : this.sample2sequence.values()) {
                    if (seq.at(pos1) == DELETION) {
                        is_subsitution = false;
                        break;
                    }
                }
            }
            Set<Allele> alleles = new HashSet<Allele>();
            VariantContextBuilder vcb = new VariantContextBuilder();
            List<Genotype> genotypes = new ArrayList<Genotype>(samples.size());
            /* longest variant */
            String longest = null;
            Counter<String> countAlleles = new Counter<String>();
            Map<String, String> sample2genotype = new HashMap<String, String>(samples.size());
            String namedConsensusRefAllele = "N";
            /* loop over the sequences of each seample */
            for (String sample : samples) {
                Sequence seq = this.sample2sequence.get(sample);
                String al = null;
                if (is_subsitution) {
                    if (seq.at(pos1) == CLIPPING)
                        continue;
                    al = String.valueOf(seq.at(pos1));
                } else {
                    StringBuilder sb = new StringBuilder(pos2 - pos1);
                    for (// yes -1
                    int i = Math.max(0, pos1 - 1); i < pos2; ++i) {
                        if (seq.at(i) == CLIPPING)
                            continue;
                        if (seq.at(i) == DELETION)
                            continue;
                        sb.append(seq.at(i));
                    }
                    if (sb.length() == 0)
                        continue;
                    al = sb.toString();
                }
                /* did we find the longest allele ?*/
                if (longest == null || longest.length() < al.length()) {
                    // reset count of most frequent, we'll use the longest indel or subst
                    countAlleles = new Counter<String>();
                    longest = al;
                }
                countAlleles.incr(al);
                sample2genotype.put(sample, al);
                /* if consensus sequence name was defined , record this allele for future use */
                if (consensusRefName != null && sample.equals(consensusRefName)) {
                    namedConsensusRefAllele = al;
                }
            }
            if (countAlleles.isEmpty()) {
                if (// printAllSites=false
                printAllSites == false) {
                    continue;
                }
                /* no a real variation, just add a dummy 'N' */
                countAlleles.incr("N");
            }
            String refAllStr;
            if (consensusRefName == null) {
                refAllStr = countAlleles.getMostFrequent();
            } else {
                refAllStr = namedConsensusRefAllele;
            }
            final Allele refAllele = Allele.create(refAllStr.replaceAll("[^ATGCatgc]", "N"), true);
            alleles.add(refAllele);
            /* loop over samples, , build each genotype */
            for (String sample : sample2genotype.keySet()) {
                Allele al = null;
                if (!sample2genotype.containsKey(sample)) {
                // nothing
                } else if (sample2genotype.get(sample).equals(refAllStr)) {
                    al = refAllele;
                } else {
                    al = Allele.create(sample2genotype.get(sample).replaceAll("[^ATGCatgc]", "N"), false);
                    alleles.add(al);
                }
                if (al != null) {
                    final GenotypeBuilder gb = new GenotypeBuilder(sample);
                    final List<Allele> sampleAlleles = new ArrayList<Allele>(2);
                    sampleAlleles.add(al);
                    if (!haploid)
                        sampleAlleles.add(al);
                    gb.alleles(sampleAlleles);
                    gb.DP(1);
                    genotypes.add(gb.make());
                } else {
                    genotypes.add(GenotypeBuilder.createMissing(sample, haploid ? 1 : 2));
                }
            }
            // got to 1-based ref if subst, for indel with use pos(base)-1
            final int start = pos1 + (is_subsitution ? 1 : 0);
            vcb.start(start);
            vcb.stop(start + (refAllStr.length() - 1));
            vcb.chr(REF);
            HashMap<String, Object> atts = new HashMap<String, Object>();
            atts.put(VCFConstants.DEPTH_KEY, genotypes.size());
            vcb.attributes(atts);
            vcb.alleles(alleles);
            vcb.genotypes(genotypes);
            w.add(vcb.make());
            pos1 = pos2;
        }
        w.close();
        if (outFasta != null) {
            final PrintWriter fasta = super.openFileOrStdoutAsPrintWriter(outFasta);
            for (final String sample : samples) {
                fasta.println(">" + sample);
                final Sequence seq = this.sample2sequence.get(sample);
                for (int i = 0; i < align_length; ++i) {
                    fasta.print(seq.at(i));
                }
                fasta.println();
            }
            fasta.println(">CONSENSUS");
            for (int i = 0; i < align_length; ++i) {
                fasta.print(consensus.at(i));
            }
            fasta.println();
            fasta.flush();
            fasta.close();
        }
        LOG.info("Done");
        return RETURN_OK;
    } catch (Exception err) {
        LOG.error(err);
        return -1;
    } finally {
        CloserUtil.close(r);
        CloserUtil.close(w);
    }
}

Example 38 with GenotypeBuilder

use of htsjdk.variant.variantcontext.GenotypeBuilder in project jvarkit by lindenb.

the class NoZeroVariationVCF method doVcfToVcf.

@Override
protected int doVcfToVcf(String inputName, VcfIterator in, VariantContextWriter out) {
    final VCFHeader header = in.getHeader();
    if (in.hasNext()) {
        LOG.info("found a variant in VCF.");
        VCFUtils.copyHeaderAndVariantsTo(in, out);
    } else {
        LOG.info("no a variant in VCF. Creating a fake Variant");
        header.addMetaDataLine(new VCFFilterHeaderLine("FAKESNP", "Fake SNP created because vcf input was empty."));
        VCFFormatHeaderLine gtHeaderLine = header.getFormatHeaderLine(VCFConstants.GENOTYPE_KEY);
        if (gtHeaderLine == null) {
            LOG.info("Adding GT to header");
            header.addMetaDataLine(new VCFFormatHeaderLine(VCFConstants.GENOTYPE_KEY, 1, VCFHeaderLineType.String, "Genotype"));
        }
        gtHeaderLine = header.getFormatHeaderLine(VCFConstants.GENOTYPE_QUALITY_KEY);
        if (gtHeaderLine == null) {
            LOG.info("Adding GQ to header");
            header.addMetaDataLine(new VCFFormatHeaderLine(VCFConstants.GENOTYPE_QUALITY_KEY, 1, VCFHeaderLineType.Integer, "Genotype Quality"));
        }
        out.writeHeader(header);
        SAMSequenceDictionary dict = this.indexedFastaSequenceFile.getSequenceDictionary();
        // choose random chrom, best is 'random' , but not 1...23,X,Y, etc...
        String chrom = dict.getSequence(0).getSequenceName();
        for (final SAMSequenceRecord ssr : dict.getSequences()) {
            String ssn = ssr.getSequenceName();
            if (ssn.contains("_")) {
                chrom = ssn;
                break;
            }
        }
        for (final SAMSequenceRecord ssr : dict.getSequences()) {
            String ssn = ssr.getSequenceName();
            if (ssn.toLowerCase().contains("random")) {
                chrom = ssn;
                break;
            }
            if (ssn.toLowerCase().contains("gl")) {
                chrom = ssn;
                break;
            }
        }
        GenomicSequence gseq = new GenomicSequence(this.indexedFastaSequenceFile, chrom);
        char ref = 'N';
        char alt = 'N';
        int POS = 0;
        for (POS = 0; POS < gseq.length(); ++POS) {
            ref = Character.toUpperCase(gseq.charAt(POS));
            if (ref == 'N')
                continue;
            switch(ref) {
                case 'A':
                    alt = 'T';
                    break;
                case 'T':
                    alt = 'G';
                    break;
                case 'G':
                    alt = 'C';
                    break;
                case 'C':
                    alt = 'A';
                    break;
                default:
                    break;
            }
            if (alt == 'N')
                continue;
            break;
        }
        if (alt == 'N')
            throw new RuntimeException("found only N");
        VariantContextBuilder vcb = new VariantContextBuilder();
        Allele a1 = Allele.create((byte) ref, true);
        Allele a2 = Allele.create((byte) alt, false);
        List<Allele> la1a2 = new ArrayList<Allele>(2);
        List<Genotype> genotypes = new ArrayList<Genotype>(header.getSampleNamesInOrder().size());
        la1a2.add(a1);
        la1a2.add(a2);
        vcb.chr(gseq.getChrom());
        vcb.start(POS + 1);
        vcb.stop(POS + 1);
        vcb.filter("FAKESNP");
        vcb.alleles(la1a2);
        vcb.log10PError(-0.1);
        for (String sample : header.getSampleNamesInOrder()) {
            final GenotypeBuilder gb = new GenotypeBuilder(sample);
            if (genotypes.isEmpty()) {
                gb.DP(1);
                gb.GQ(1);
                gb.alleles(la1a2);
                gb.noAD();
                gb.noPL();
                genotypes.add(gb.make());
            } else {
                genotypes.add(GenotypeBuilder.createMissing(sample, 2));
            }
        }
        vcb.genotypes(genotypes);
        vcb.noID();
        out.add(vcb.make());
    }
    return 0;
}

Example 39 with GenotypeBuilder

use of htsjdk.variant.variantcontext.GenotypeBuilder in project jvarkit by lindenb.

the class VcfRenameSamples method doVcfToVcf.

@Override
protected int doVcfToVcf(String inputName, VcfIterator in, VariantContextWriter out) {
    final VCFHeader header1 = in.getHeader();
    final Set<String> samples1 = new LinkedHashSet<String>(header1.getSampleNamesInOrder());
    final List<String> newHeader = new ArrayList<String>(samples1);
    for (int i = 0; i < newHeader.size(); ++i) {
        final String destName = this.oldNameToNewName.get(newHeader.get(i));
        if (destName == null)
            continue;
        newHeader.set(i, destName);
    }
    if (newHeader.size() != new HashSet<String>(newHeader).size()) {
        throw new RuntimeException("Error in input : there are some diplicates in the resulting new VCF header: " + newHeader);
    }
    for (final String srcName : this.oldNameToNewName.keySet()) {
        if (!samples1.contains(srcName)) {
            if (missing_user_name_is_error) {
                LOG.error("Source Sample " + srcName + " missing in " + samples1 + ". Use option -E to ignore");
                return -1;
            } else {
                LOG.warning("Missing src-sample:" + srcName);
            }
        }
    }
    final VCFHeader header2 = new VCFHeader(header1.getMetaDataInInputOrder(), newHeader);
    header2.addMetaDataLine(new VCFHeaderLine(getClass().getSimpleName() + "CmdLine", String.valueOf(getProgramCommandLine())));
    header2.addMetaDataLine(new VCFHeaderLine(getClass().getSimpleName() + "Version", String.valueOf(getVersion())));
    header2.addMetaDataLine(new VCFHeaderLine(getClass().getSimpleName() + "HtsJdkVersion", HtsjdkVersion.getVersion()));
    header2.addMetaDataLine(new VCFHeaderLine(getClass().getSimpleName() + "HtsJdkHome", HtsjdkVersion.getHome()));
    out.writeHeader(header2);
    final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(header1);
    while (in.hasNext()) {
        final VariantContext ctx = progress.watch(in.next());
        final VariantContextBuilder b = new VariantContextBuilder(ctx);
        final List<Genotype> genotypes = new ArrayList<Genotype>();
        for (final String oldName : samples1) {
            Genotype g = ctx.getGenotype(oldName);
            final String destName = this.oldNameToNewName.get(oldName);
            if (destName != null) {
                final GenotypeBuilder gb = new GenotypeBuilder(g);
                gb.name(destName);
                g = gb.make();
            }
            genotypes.add(g);
        }
        b.genotypes(genotypes);
        out.add(b.make());
    }
    progress.finish();
    return 0;
}

Example 40 with GenotypeBuilder

use of htsjdk.variant.variantcontext.GenotypeBuilder in project jvarkit by lindenb.

the class VCFCompareGT method doWork.

@Override
public int doWork(final List<String> arguments) {
    final List<File> inputVcfFiles = new ArrayList<>(IOUtil.unrollFiles(arguments.stream().map(F -> new File(F)).collect(Collectors.toCollection(HashSet::new)), ".vcf", "vcf.gz"));
    if (inputVcfFiles.isEmpty()) {
        LOG.error("VCF missing.");
        return -1;
    }
    VariantComparator varcmp = new VariantComparator();
    SortingCollection<Variant> variants = null;
    final Set<String> sampleNames = new LinkedHashSet<>();
    try {
        variants = SortingCollection.newInstance(Variant.class, new VariantCodec(), varcmp, writingSortingCollection.getMaxRecordsInRam(), writingSortingCollection.getTmpPaths());
        variants.setDestructiveIteration(true);
        final Set<VCFHeaderLine> metaData = new HashSet<VCFHeaderLine>();
        metaData.add(new VCFHeaderLine(getClass().getSimpleName(), "version:" + getVersion() + " command:" + getProgramCommandLine()));
        for (int i = 0; i < inputVcfFiles.size(); ++i) {
            final File vcfFile = inputVcfFiles.get(i);
            LOG.info("Opening " + vcfFile);
            final VCFFileReader vcfFileReader = new VCFFileReader(vcfFile, false);
            final CloseableIterator<VariantContext> iter = vcfFileReader.iterator();
            final VCFHeader header = vcfFileReader.getFileHeader();
            sampleNames.addAll(header.getSampleNamesInOrder());
            metaData.add(new VCFHeaderLine(getClass().getSimpleName() + "_" + ((i) + 1), "File: " + vcfFile.getPath()));
            long nLines = 0;
            while (iter.hasNext()) {
                final VariantContext var = iter.next();
                if (nLines++ % 10000 == 0) {
                    LOG.info(vcfFile + " " + nLines);
                }
                if (!var.isVariant())
                    continue;
                if (!var.hasGenotypes())
                    continue;
                for (final Genotype genotype : var.getGenotypes()) {
                    final Variant rec = new Variant();
                    if (!genotype.isAvailable())
                        continue;
                    if (!genotype.isCalled())
                        continue;
                    if (genotype.isNoCall())
                        continue;
                    rec.file_index = i + 1;
                    rec.sampleName = genotype.getSampleName();
                    rec.chrom = var.getContig();
                    rec.start = var.getStart();
                    rec.end = var.getEnd();
                    rec.ref = var.getReference().getDisplayString();
                    if (var.hasID()) {
                        rec.id = var.getID();
                    }
                    if (genotype.hasDP()) {
                        rec.dp = genotype.getDP();
                    }
                    if (genotype.hasGQ()) {
                        rec.gq = genotype.getGQ();
                    }
                    final List<Allele> alleles = genotype.getAlleles();
                    if (alleles == null)
                        continue;
                    if (alleles.size() == 1) {
                        rec.a1 = alleles.get(0).getDisplayString().toUpperCase();
                        rec.a2 = rec.a1;
                    } else if (alleles.size() == 2) {
                        rec.a1 = alleles.get(0).getDisplayString().toUpperCase();
                        rec.a2 = alleles.get(1).getDisplayString().toUpperCase();
                        if (rec.a1.compareTo(rec.a2) > 0) {
                            String tmp = rec.a2;
                            rec.a2 = rec.a1;
                            rec.a1 = tmp;
                        }
                    } else {
                        continue;
                    }
                    variants.add(rec);
                }
            }
            iter.close();
            vcfFileReader.close();
        }
        variants.doneAdding();
        LOG.info("Done Adding");
        final Set<String> newSampleNames = new HashSet<>();
        for (int i = 0; i < inputVcfFiles.size(); ++i) {
            for (final String sample : sampleNames) {
                newSampleNames.add(sample + "_" + ((i) + 1));
            }
        }
        final String GenpotypeChangedKey = "GCH";
        final String GenpotypeCreated = "GNW";
        final String GenpotypeDiff = "GDF";
        metaData.add(new VCFFormatHeaderLine(VCFConstants.GENOTYPE_KEY, 1, VCFHeaderLineType.String, "Genotype"));
        metaData.add(new VCFFormatHeaderLine("DP", 1, VCFHeaderLineType.Integer, "Depth"));
        metaData.add(new VCFFormatHeaderLine(VCFConstants.GENOTYPE_QUALITY_KEY, 1, VCFHeaderLineType.Integer, "Qual"));
        metaData.add(new VCFFormatHeaderLine(GenpotypeChangedKey, 1, VCFHeaderLineType.Integer, "Changed Genotype"));
        metaData.add(new VCFFormatHeaderLine(GenpotypeCreated, 1, VCFHeaderLineType.Integer, "Genotype Created/Deleted"));
        metaData.add(new VCFInfoHeaderLine(GenpotypeDiff, VCFHeaderLineCount.UNBOUNDED, VCFHeaderLineType.String, "Samples with Genotype Difference"));
        final VCFHeader header = new VCFHeader(metaData, new ArrayList<String>(newSampleNames));
        final VariantContextWriter w = super.openVariantContextWriter(outputFile);
        w.writeHeader(header);
        final PosComparator posCompare = new PosComparator();
        final EqualRangeIterator<Variant> iter = new EqualRangeIterator<>(variants.iterator(), posCompare);
        while (iter.hasNext()) {
            final List<Variant> row = iter.next();
            /**
             * this sample is not always the same
             */
            final Set<String> samplesModified = new TreeSet<>();
            /**
             * the number of sample is different from vcflist.size()
             */
            final Set<String> samplesCreates = new TreeSet<>();
            final Counter<String> samplesSeen = new Counter<>();
            for (int x = 0; x < row.size(); ++x) {
                final Variant var1 = row.get(x);
                samplesSeen.incr(var1.sampleName);
                for (int y = x + 1; y < row.size(); ++y) {
                    final Variant var2 = row.get(y);
                    if (!var2.sampleName.equals(var1.sampleName))
                        continue;
                    if (var1.a1.equals(var2.a1) && var1.a2.equals(var2.a2))
                        continue;
                    samplesModified.add(var1.sampleName);
                }
            }
            for (final String sampleName : samplesSeen.keySet()) {
                if (samplesSeen.count(sampleName) != inputVcfFiles.size()) {
                    samplesCreates.add(sampleName);
                }
            }
            final Variant first = row.get(0);
            final Set<Allele> alleles = new HashSet<>();
            alleles.add(Allele.create(first.ref, true));
            for (final Variant var : row) {
                alleles.add(Allele.create(var.a1, var.a1.equalsIgnoreCase(var.ref)));
                alleles.add(Allele.create(var.a2, var.a2.equalsIgnoreCase(var.ref)));
            }
            final VariantContextBuilder b = new VariantContextBuilder(getClass().getName(), first.chrom, first.start, first.end, alleles);
            // build genotypes
            final List<Genotype> genotypes = new ArrayList<Genotype>();
            for (final Variant var : row) {
                // alleles for this genotype
                final List<Allele> galleles = new ArrayList<Allele>();
                galleles.add(Allele.create(var.a1, var.a1.equalsIgnoreCase(var.ref)));
                galleles.add(Allele.create(var.a2, var.a2.equalsIgnoreCase(var.ref)));
                final GenotypeBuilder gb = new GenotypeBuilder();
                gb.DP(var.dp);
                gb.alleles(galleles);
                gb.name(var.sampleName + "_" + var.file_index);
                gb.GQ(var.gq);
                gb.attribute(GenpotypeChangedKey, samplesModified.contains(var.sampleName) ? 1 : 0);
                gb.attribute(GenpotypeCreated, samplesCreates.contains(var.sampleName) ? 1 : 0);
                genotypes.add(gb.make());
            }
            b.genotypes(genotypes);
            b.id(first.id);
            if (!(samplesModified.isEmpty() && samplesCreates.isEmpty())) {
                Set<String> set2 = new TreeSet<String>(samplesModified);
                set2.addAll(samplesCreates);
                b.attribute(GenpotypeDiff, set2.toArray());
            }
            if (!only_print_modified || !(samplesModified.isEmpty() && samplesCreates.isEmpty())) {
                w.add(b.make());
            }
        }
        iter.close();
        w.close();
    } catch (final Exception err) {
        LOG.error(err);
        return -1;
    } finally {
        if (variants != null)
            try {
                variants.cleanup();
            } catch (Exception err) {
            }
    }
    return 0;
}