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

Example 46 with Allele

use of htsjdk.variant.variantcontext.Allele in project ASCIIGenome by dariober.

the class GenotypeMatrix method genotypeAsAlleleIndexes.

/**
 * Get the sample genotype in the same format as it appears on the VCF file.
 * I.e. allele indexes separated by '/' or '|' (if phased). E.g. 0/0, 0/1 etc
 */
private String genotypeAsAlleleIndexes(VariantContext ctx, String sample) {
    Genotype gt = ctx.getGenotype(sample);
    char sep = gt.isPhased() ? '|' : '/';
    List<String> all = new ArrayList<String>();
    for (Allele a : gt.getAlleles()) {
        if (a.isNoCall()) {
            all.add(".");
        } else {
            int i = ctx.getAlleleIndex(a);
            all.add(Integer.toString(i));
        }
    }
    return '"' + Joiner.on(sep).join(all) + '"';
}

Example 47 with Allele

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

the class Biostar175929 method recursive.

private void recursive(final GenomicSequence chromosome, final List<VariantContext> variants, int index, StringBuilder title, StringBuilder sequence) {
    if (index == variants.size()) {
        int lastPos0 = (variants.get(index - 1).getEnd() - 1);
        for (int i = 0; i < this.extendBases && lastPos0 + i < chromosome.length(); ++i) {
            sequence.append(Character.toLowerCase(chromosome.charAt(lastPos0 + i)));
        }
        pw.print(">");
        pw.print(title);
        for (int i = 0; i < sequence.length(); ++i) {
            if (i % 60 == 0)
                pw.println();
            pw.print(sequence.charAt(i));
        }
        pw.println();
        return;
    }
    if (index == 0) {
        int firstPos0 = (variants.get(0).getStart() - 1);
        int chromStart = Math.max(0, firstPos0 - extendBases);
        title.append(variants.get(0).getContig() + ":" + chromStart);
        for (int i = Math.max(0, firstPos0 - extendBases); i < firstPos0; ++i) {
            sequence.append(Character.toLowerCase(chromosome.charAt(i)));
        }
    } else {
        int endPos0 = (variants.get(index - 1).getEnd());
        int begPos0 = (variants.get(index).getStart() - 1);
        while (endPos0 < begPos0) {
            sequence.append(Character.toLowerCase(chromosome.charAt(endPos0)));
            endPos0++;
        }
    }
    final int title_length = title.length();
    final int sequence_length = sequence.length();
    final VariantContext ctx = variants.get(index);
    for (final Allele allele : ctx.getAlleles()) {
        if (allele.isNoCall())
            continue;
        if (allele.isSymbolic())
            continue;
        title.setLength(title_length);
        sequence.setLength(sequence_length);
        title.append("|" + ctx.getContig() + ":" + ctx.getStart() + "-" + ctx.getEnd() + "(" + allele.getBaseString() + ")");
        if (this.bracket)
            sequence.append("[");
        sequence.append(allele.getBaseString().toUpperCase());
        if (this.bracket)
            sequence.append("]");
        recursive(chromosome, variants, index + 1, title, sequence);
    }
}

Example 48 with Allele

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

the class HaloplexParasite method doVcfToVcf.

@Override
protected int doVcfToVcf(String inputName, VcfIterator in, VariantContextWriter out) {
    SamReader samReader = null;
    final List<Mutation> mutations = new ArrayList<>();
    try {
        final Set<File> bamFiles = Files.lines(this.bamList.toPath()).filter(T -> !(T.isEmpty() || T.startsWith("#"))).map(T -> new File(T)).collect(Collectors.toSet());
        final VCFHeader header = new VCFHeader();
        header.setSequenceDictionary(in.getHeader().getSequenceDictionary());
        final VCFFilterHeaderLine filter = new VCFFilterHeaderLine("HALOPLEXPARASITE", "fails Parasite Haloplex Sequence");
        final VCFInfoHeaderLine infoWord = new VCFInfoHeaderLine(filter.getID(), 1, VCFHeaderLineType.String, "Parasite Haloplex Sequence (Word|Count|Fraction)");
        super.addMetaData(header);
        out.writeHeader(header);
        header.addMetaDataLine(filter);
        header.addMetaDataLine(infoWord);
        while (in.hasNext()) {
            final VariantContext ctx = in.next();
            final VariantContextBuilder vcb = new VariantContextBuilder(inputName, ctx.getContig(), ctx.getStart(), ctx.getEnd(), ctx.getAlleles());
            if (!(ctx.isIndel() || ctx.isMixed())) {
                out.add(vcb.make());
                continue;
            }
            if (!vcb.getAlleles().stream().filter(A -> !(A.isSymbolic() || A.isNoCall() || A.length() < this.minClipSize)).findAny().isPresent()) {
                out.add(vcb.make());
                continue;
            }
            final Mutation mut = new Mutation(ctx);
            mutations.add(mut);
        }
        final Counter<String> words = new Counter<>();
        for (final File bamFile : bamFiles) {
            LOG.info("Opening " + bamFile);
            samReader = createSamReaderFactory().open(bamFile);
            for (final Mutation mut : mutations) {
                // words seen in that mutation : don't use a Counter
                final Set<String> mutWords = new HashSet<>();
                /* loop over reads overlapping that mutation */
                final SAMRecordIterator sri = samReader.queryOverlapping(mut.contig, mut.start, mut.end);
                while (sri.hasNext()) {
                    final SAMRecord rec = sri.next();
                    if (rec.getReadUnmappedFlag())
                        continue;
                    if (rec.isSecondaryOrSupplementary())
                        continue;
                    if (rec.getDuplicateReadFlag())
                        continue;
                    if (rec.getReadFailsVendorQualityCheckFlag())
                        continue;
                    final Cigar cigar = rec.getCigar();
                    if (cigar.numCigarElements() == 1)
                        continue;
                    final byte[] bases = rec.getReadBases();
                    int refpos = rec.getUnclippedStart();
                    int readpos = 0;
                    /* scan cigar overlapping that mutation */
                    for (final CigarElement ce : cigar) {
                        final CigarOperator op = ce.getOperator();
                        final int ref_end = refpos + (op.consumesReferenceBases() || op.isClipping() ? ce.getLength() : 0);
                        final int read_end = readpos + (op.consumesReadBases() ? ce.getLength() : 0);
                        /* check clip is large enough */
                        if (op.equals(CigarOperator.S) && ce.getLength() >= this.minClipSize) {
                            /* check clip overlap mutation */
                            if (!(ref_end < mut.start || refpos > mut.end)) {
                                /* break read of soft clip into words */
                                for (int x = 0; x + this.minClipSize <= ce.getLength(); ++x) {
                                    final String substr = new String(bases, readpos + x, this.minClipSize);
                                    if (!substr.contains("N")) {
                                        final String revcomp = AcidNucleics.reverseComplement(substr);
                                        mutWords.add(substr);
                                        if (!revcomp.equals(substr))
                                            mutWords.add(revcomp);
                                    }
                                }
                            }
                        }
                        refpos = ref_end;
                        readpos = read_end;
                    }
                }
                sri.close();
                for (final String w : mutWords) {
                    words.incr(w);
                }
            }
            // end of for(mutations)
            samReader.close();
            samReader = null;
        }
        LOG.info("mutations:" + mutations.size());
        final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(header);
        for (final Mutation mut : mutations) {
            progress.watch(mut.contig, mut.start);
            final VariantContextBuilder vcb = new VariantContextBuilder(inputName, mut.contig, mut.start, mut.end, mut.alleles);
            String worstString = null;
            Double worstFraction = null;
            final double totalWords = words.getTotal();
            for (final Allele a : mut.alleles) {
                if (a.isSymbolic() || a.isNoCall() || a.length() < this.minClipSize)
                    continue;
                for (int x = 0; x + this.minClipSize <= a.length(); ++x) {
                    final String substr = new String(a.getBases(), x, this.minClipSize);
                    final long count = words.count(substr);
                    final double fraction = count / totalWords;
                    if (worstFraction == null || worstFraction < fraction) {
                        worstString = substr + "|" + count + "|" + fraction;
                        worstFraction = fraction;
                    }
                }
            }
            if (worstString != null) {
                vcb.attribute(infoWord.getID(), worstString);
            }
            if (worstFraction != null && worstFraction.doubleValue() >= this.tresholdFraction) {
                vcb.filter(filter.getID());
            }
            out.add(vcb.make());
        }
        progress.finish();
        return RETURN_OK;
    } catch (Exception e) {
        LOG.error(e);
        return -1;
    } finally {
        CloserUtil.close(samReader);
    }
}

Example 49 with Allele

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

the class VcfDoest method run.

private void run(final LineIterator lr, final PrintWriter pw) throws IOException {
    SortingCollection<TranscriptInfo> sorting = null;
    CloseableIterator<TranscriptInfo> iter2 = null;
    try {
        while (lr.hasNext()) {
            VcfIterator in = VCFUtils.createVcfIteratorFromLineIterator(lr, true);
            final VCFHeader header = in.getHeader();
            final Pedigree pedigree = Pedigree.newParser().parse(header);
            if (pedigree.isEmpty()) {
                throw new IOException("No pedigree found in header VCF header. use VcfInjectPedigree to add it");
            }
            final SortedSet<Pedigree.Person> individuals = new TreeSet<>();
            for (final Pedigree.Person individual : pedigree.getPersons()) {
                if (individual.isAffected() || individual.isUnaffected()) {
                    individuals.add(individual);
                }
            }
            boolean first = true;
            pw.println("# samples ( 0: unaffected 1:affected)");
            pw.print("population <- data.frame(family=c(");
            first = true;
            for (final Pedigree.Person person : individuals) {
                if (!first)
                    pw.print(",");
                pw.print("\"" + person.getFamily().getId() + "\"");
                first = false;
            }
            pw.print("),name=c(");
            first = true;
            for (final Pedigree.Person person : individuals) {
                if (!first)
                    pw.print(",");
                pw.print("\"" + person.getId() + "\"");
                first = false;
            }
            pw.print("),status=c(");
            first = true;
            for (final Pedigree.Person person : individuals) {
                if (!first)
                    pw.print(",");
                pw.print(person.isUnaffected() ? 0 : 1);
                first = false;
            }
            pw.println("))");
            sorting = SortingCollection.newInstance(TranscriptInfo.class, new TranscriptInfoCodec(), new TranscriptInfoCmp(), this.writingSortingCollection.getMaxRecordsInRam(), this.writingSortingCollection.getTmpPaths());
            sorting.setDestructiveIteration(true);
            final SAMSequenceDictionaryProgress progess = new SAMSequenceDictionaryProgress(header.getSequenceDictionary());
            /**
             * loop over variants
             */
            while (in.hasNext() && !pw.checkError()) {
                final VariantContext ctx = progess.watch(in.next());
                if (ctx.isFiltered())
                    continue;
                if (ctx.getAlternateAlleles().isEmpty())
                    continue;
                final Allele altAllele = ctx.getAltAlleleWithHighestAlleleCount();
                final MafCalculator mafCalculator = new MafCalculator(altAllele, ctx.getContig());
                boolean genotyped = false;
                for (final Pedigree.Person p : pedigree.getPersons()) {
                    if (!(p.isAffected() || p.isUnaffected()))
                        continue;
                    final Genotype g = ctx.getGenotype(p.getId());
                    if (g == null)
                        throw new IOException("Strange I cannot find individual " + p + " in the pedigree. Aborting.");
                    if (g.isCalled()) {
                        mafCalculator.add(g, p.isMale());
                    }
                    if (g.isHet() || g.isHomVar()) {
                        if (!g.getAlleles().contains(altAllele))
                            continue;
                        genotyped = true;
                        break;
                    }
                }
                if (!genotyped)
                    continue;
                final Interval interval = new Interval(ctx.getContig(), ctx.getStart(), ctx.getEnd());
                final List<KnownGene> genes = this.overlap(interval);
                if (genes.isEmpty())
                    continue;
                for (final KnownGene kg : genes) {
                    final TranscriptInfo trInfo = new TranscriptInfo();
                    trInfo.contig = kg.getContig();
                    trInfo.txStart = kg.getTxStart();
                    trInfo.txEnd = kg.getTxEnd();
                    trInfo.transcriptName = kg.getName();
                    trInfo.strand = (byte) (kg.isPositiveStrand() ? '+' : '-');
                    trInfo.exonCount = kg.getExonCount();
                    trInfo.transcriptLength = kg.getTranscriptLength();
                    trInfo.ctxStart = ctx.getStart();
                    trInfo.ref = ctx.getReference();
                    trInfo.alt = altAllele;
                    trInfo.maf = mafCalculator.getMaf();
                    trInfo.genotypes = new byte[individuals.size()];
                    int idx = 0;
                    for (final Pedigree.Person individual : individuals) {
                        final Genotype genotype = ctx.getGenotype(individual.getId());
                        final byte b;
                        if (genotype.isHomRef()) {
                            b = 0;
                        } else if (genotype.isHomVar() && genotype.getAlleles().contains(altAllele)) {
                            b = 2;
                        } else if (genotype.isHet() && genotype.getAlleles().contains(altAllele) && genotype.getAlleles().contains(ctx.getReference())) {
                            b = 1;
                        } else /* we treat 0/2 has hom-ref */
                        if (genotype.isHet() && !genotype.getAlleles().contains(altAllele) && genotype.getAlleles().contains(ctx.getReference())) {
                            LOG.warn("Treating " + genotype + " as hom-ref (0) alt=" + altAllele);
                            b = 0;
                        } else /* we treat 2/2 has hom-ref */
                        if (genotype.isHomVar() && !genotype.getAlleles().contains(altAllele)) {
                            LOG.warn("Treating " + genotype + " as hom-ref (0) alt=" + altAllele);
                            b = 0;
                        } else {
                            b = -9;
                        }
                        trInfo.genotypes[idx] = b;
                        ++idx;
                    }
                    KnownGene archetype = kg;
                    /* find gene archetype = longest overlapping */
                    for (final KnownGene kg2 : genes) {
                        if (kg2 == kg)
                            continue;
                        if (archetype.getStrand().equals(kg2.getStrand()) && archetype.getTranscriptLength() < kg2.getTranscriptLength()) {
                            archetype = kg2;
                        }
                    }
                    trInfo.archetypeName = archetype.getName();
                    trInfo.archetypeLength = archetype.getTranscriptLength();
                    boolean ctxWasFoundInExon = false;
                    final int ctxPos0 = ctx.getStart() - 1;
                    int indexInTranscript0 = 0;
                    for (final KnownGene.Exon exon : kg.getExons()) {
                        // variant in exon ?
                        if (!(exon.getStart() > (ctx.getEnd() - 1) || (ctx.getStart() - 1) >= exon.getEnd())) {
                            ctxWasFoundInExon = true;
                            indexInTranscript0 += (ctxPos0 - exon.getStart());
                            if (kg.isNegativeStrand()) {
                                indexInTranscript0 = (kg.getTranscriptLength() - 1) - indexInTranscript0;
                            }
                            trInfo.indexInTranscript0 = indexInTranscript0;
                            trInfo.overlapName = exon.getName();
                            sorting.add(trInfo);
                            break;
                        } else {
                            indexInTranscript0 += (exon.getEnd() - exon.getStart());
                        }
                    }
                    if (ctxWasFoundInExon) {
                        continue;
                    }
                    indexInTranscript0 = 0;
                    // search closest intron/exon junction
                    for (int ex = 0; ex + 1 < kg.getExonCount(); ++ex) {
                        final KnownGene.Exon exon1 = kg.getExon(ex);
                        indexInTranscript0 += (exon1.getEnd() - exon1.getStart());
                        final KnownGene.Exon exon2 = kg.getExon(ex + 1);
                        if (exon1.getEnd() <= ctxPos0 && ctxPos0 < exon2.getStart()) {
                            final int dist_to_exon1 = ctxPos0 - exon1.getEnd();
                            final int dist_to_exon2 = exon2.getStart() - ctxPos0;
                            if (dist_to_exon2 < dist_to_exon1) {
                                indexInTranscript0++;
                            }
                            if (kg.isNegativeStrand()) {
                                indexInTranscript0 = (kg.getTranscriptLength() - 1) - indexInTranscript0;
                            }
                            trInfo.indexInTranscript0 = indexInTranscript0;
                            trInfo.overlapName = exon1.getNextIntron().getName();
                            sorting.add(trInfo);
                            break;
                        }
                    }
                }
            // end loop over genes
            }
            // end while loop over variants
            progess.finish();
            sorting.doneAdding();
            LOG.info("done adding");
            iter2 = sorting.iterator();
            final EqualRangeIterator<TranscriptInfo> eqiter = new EqualRangeIterator<TranscriptInfo>(iter2, new Comparator<TranscriptInfo>() {

                @Override
                public int compare(final TranscriptInfo o1, final TranscriptInfo o2) {
                    int i = o1.contig.compareTo(o2.contig);
                    if (i != 0)
                        return i;
                    i = o1.transcriptName.compareTo(o2.transcriptName);
                    return i;
                }
            });
            while (eqiter.hasNext()) {
                final List<TranscriptInfo> list = eqiter.next();
                final TranscriptInfo front = list.get(0);
                pw.println("# BEGIN TRANSCRIPT " + front.transcriptName + " ##########################################");
                pw.println("transcript.chrom <- \"" + front.contig + "\"");
                pw.println("transcript.txStart0 <- " + front.txStart + "");
                pw.println("transcript.txEnd0 <- " + front.txEnd + "");
                pw.println("transcript.name <- \"" + front.transcriptName + "\"");
                pw.println("transcript.strand <- \"" + ((char) front.strand) + "\"");
                pw.println("transcript.length <- " + front.transcriptLength + "");
                pw.println("transcript.exonCount <- " + front.exonCount + "");
                pw.println("archetype.name <- \"" + front.archetypeName + "\"");
                pw.println("archetype.length <- " + front.archetypeLength + "");
                pw.print("variants <- data.frame(chrom=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print("\"" + v.contig + "\"");
                    first = false;
                }
                pw.print("),chromStart=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print(v.ctxStart);
                    first = false;
                }
                pw.print("),chromEnd=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print(v.ctxStart + v.ref.length() - 1);
                    first = false;
                }
                pw.print("),refAllele=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print("\"" + v.ref.getDisplayString() + "\"");
                    first = false;
                }
                pw.print("),altAllele=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print("\"" + v.alt.getDisplayString() + "\"");
                    first = false;
                }
                pw.print("),positionInTranscript1=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print(v.indexInTranscript0 + 1);
                    first = false;
                }
                pw.print("),maf=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print(v.maf);
                    first = false;
                }
                pw.print("),overlapName=c(");
                first = true;
                for (final TranscriptInfo v : list) {
                    if (!first)
                        pw.print(",");
                    pw.print("\"" + v.overlapName + "\"");
                    first = false;
                }
                pw.println("))");
                pw.println("# genotypes as a list. Should be a multiple of length(samples).");
                pw.println("# 0 is homref (0/0), 1 is het (0/1), 2 is homvar (1/1)");
                pw.println("# if the variant contains another ALT allele: (0/2) and (2/2) are considered 0 (homref)");
                pw.print("genotypes <- c(");
                first = true;
                for (final TranscriptInfo tr : list) {
                    for (byte g : tr.genotypes) {
                        if (!first)
                            pw.print(",");
                        first = false;
                        pw.print((int) g);
                    }
                }
                pw.println(")");
                pw.println("stopifnot(NROW(variants) * NROW(population) == length(genotypes) )");
                if (this.userDefinedFunName == null || this.userDefinedFunName.trim().isEmpty()) {
                    pw.println("## WARNING not user-defined R function was defined");
                } else {
                    pw.println("# consumme data with user-defined R function ");
                    pw.println(this.userDefinedFunName + "()");
                }
                pw.println("# END TRANSCRIPT " + front.transcriptName + " ##########################################");
            }
            // end while eqiter
            eqiter.close();
            iter2.close();
            iter2 = null;
            sorting.cleanup();
            sorting = null;
        }
    } finally {
        CloserUtil.close(iter2);
        if (sorting != null)
            sorting.cleanup();
    }
}

Example 50 with Allele

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

the class VcfAnnotWithBeacon method doVcfToVcf.

@Override
protected int doVcfToVcf(String inputName, final VcfIterator iter, final VariantContextWriter out) {
    CloseableHttpClient httpClient = null;
    InputStream contentInputStream = null;
    try {
        final org.apache.http.impl.client.HttpClientBuilder hb = HttpClients.custom();
        if (this.ignoreCertErrors) {
            // http://stackoverflow.com/questions/24720013/apache-http-client-ssl-certificate-error
            System.setProperty("jsse.enableSNIExtension", "false");
            final SSLContext sslContext = org.apache.http.conn.ssl.SSLContexts.custom().loadTrustMaterial(null, new org.apache.http.conn.ssl.TrustStrategy() {

                @Override
                public boolean isTrusted(final X509Certificate[] chain, final String authType) throws CertificateException {
                    return true;
                }
            }).useTLS().build();
            final org.apache.http.conn.ssl.SSLConnectionSocketFactory connectionFactory = new org.apache.http.conn.ssl.SSLConnectionSocketFactory(sslContext, new org.apache.http.conn.ssl.AllowAllHostnameVerifier());
            hb.setSSLSocketFactory(connectionFactory);
        }
        httpClient = hb.build();
        HttpGet httpGetRequest = null;
        final Set<String> available_chromosomes = new HashSet<>();
        try {
            httpGetRequest = new HttpGet(baseurl + "/chromosomes");
            httpGetRequest.setHeader("Accept", ContentType.APPLICATION_JSON.getMimeType());
            contentInputStream = httpClient.execute(httpGetRequest).getEntity().getContent();
            JsonParser jsonparser = new JsonParser();
            final JsonElement root = jsonparser.parse(new InputStreamReader(contentInputStream));
            Iterator<JsonElement> jsr = root.getAsJsonArray().iterator();
            while (jsr.hasNext()) {
                final String ctg = jsr.next().getAsString();
                available_chromosomes.add(ctg);
            }
            LOG.debug(available_chromosomes);
        } catch (final Exception err) {
            LOG.error(err);
            return -1;
        } finally {
            CloserUtil.close(contentInputStream);
        }
        final Set<String> available_alleles = new HashSet<>();
        try {
            httpGetRequest = new HttpGet(baseurl + "/alleles");
            httpGetRequest.setHeader("Accept", ContentType.APPLICATION_JSON.getMimeType());
            contentInputStream = httpClient.execute(httpGetRequest).getEntity().getContent();
            JsonParser jsonparser = new JsonParser();
            final JsonElement root = jsonparser.parse(new InputStreamReader(contentInputStream));
            Iterator<JsonElement> jsr = root.getAsJsonArray().iterator();
            while (jsr.hasNext()) {
                final String allele = jsr.next().getAsString();
                available_alleles.add(allele);
            }
            LOG.debug(available_alleles);
        } catch (final Exception err) {
            LOG.error(err);
            return -1;
        } finally {
            CloserUtil.close(contentInputStream);
        }
        final StoredResponseBinding storedResponseBinding = new StoredResponseBinding();
        final VCFHeader header = new VCFHeader(iter.getHeader());
        final VCFInfoHeaderLine infoHeaderLine = new VCFInfoHeaderLine(this.infoTag, VCFHeaderLineCount.UNBOUNDED, VCFHeaderLineType.String, "Tag inserted with " + getProgramName());
        header.addMetaDataLine(infoHeaderLine);
        DatabaseEntry key = new DatabaseEntry();
        DatabaseEntry data = new DatabaseEntry();
        out.writeHeader(header);
        while (iter.hasNext()) {
            final VariantContext ctx = iter.next();
            if (!ctx.isVariant() || ctx.getReference().isSymbolic()) {
                out.add(ctx);
                continue;
            }
            if (ctx.hasAttribute(infoHeaderLine.getID()) && this.dontUpdateIfInfoIsPresent) {
                out.add(ctx);
                continue;
            }
            String beaconContig = ctx.getContig();
            if (!available_chromosomes.contains(beaconContig)) {
                if (beaconContig.startsWith("chr")) {
                    beaconContig = beaconContig.substring(3);
                }
                if (!available_chromosomes.contains(beaconContig)) {
                    out.add(ctx);
                    continue;
                }
            }
            final List<Allele> altAlleles = ctx.getAlternateAlleles();
            if (altAlleles.isEmpty()) {
                out.add(ctx);
                continue;
            }
            final Set<String> newInfo = new HashSet<>();
            for (final Allele alt : altAlleles) {
                if (alt.isSymbolic() || alt.isNoCall())
                    continue;
                final StringBuilder buildUrl = new StringBuilder();
                buildUrl.append("chrom=");
                buildUrl.append(URLEncoder.encode(beaconContig, "UTF-8"));
                buildUrl.append("&pos=");
                /*
					 * "Coordinate within a chromosome. Position is a number and is 0-based"
					 * .
					 */
                buildUrl.append(ctx.getStart() - 1);
                buildUrl.append("&allele=");
                final String allele;
                if (ctx.getReference().length() > alt.length()) {
                    // del
                    allele = "D";
                } else if (ctx.getReference().length() > alt.length()) {
                    // ins
                    allele = "I";
                } else {
                    allele = alt.getDisplayString();
                }
                if (!available_alleles.contains(allele))
                    continue;
                buildUrl.append(allele);
                buildUrl.append("&ref=");
                buildUrl.append(URLEncoder.encode(this.genomeBuild, "UTF-8"));
                final String queryUrl = buildUrl.toString();
                boolean foundInBdb = false;
                Set<String> foundIn = null;
                if (this.beaconDatabase != null) {
                    StringBinding.stringToEntry(queryUrl, key);
                    if (this.beaconDatabase.get(this.txn, key, data, LockMode.DEFAULT) == OperationStatus.SUCCESS) {
                        StoredResponse response = storedResponseBinding.entryToObject(data);
                        if (// TODO check how old is
                        response.timeStamp < 0) // that data
                        {
                            response = null;
                            this.beaconDatabase.delete(this.txn, key);
                        }
                        if (response != null) {
                            foundInBdb = true;
                            foundIn = response.foundIn;
                        }
                    }
                }
                if (foundIn == null) {
                    foundIn = new HashSet<>();
                    try {
                        httpGetRequest = new HttpGet(baseurl + "/responses?" + queryUrl);
                        httpGetRequest.setHeader("Accept", ContentType.APPLICATION_JSON.getMimeType());
                        LOG.debug(httpGetRequest.getURI());
                        contentInputStream = httpClient.execute(httpGetRequest).getEntity().getContent();
                        JsonParser jsonparser = new JsonParser();
                        final JsonElement root = jsonparser.parse(new InputStreamReader(contentInputStream));
                        Iterator<JsonElement> jsr = root.getAsJsonArray().iterator();
                        while (jsr.hasNext()) {
                            final JsonObject b = jsr.next().getAsJsonObject();
                            if (!(b.has("beacon") && b.has("response")))
                                continue;
                            final String beacon_id = b.get("beacon").getAsJsonObject().get("id").getAsString();
                            final JsonElement response_prim = b.get("response");
                            if (response_prim.isJsonPrimitive() && response_prim.getAsBoolean()) {
                                foundIn.add(beacon_id);
                            }
                        }
                    } catch (final Exception err) {
                        LOG.error(err);
                        if (stopOnNetworkError) {
                            throw new RuntimeIOException(err);
                        }
                    } finally {
                        CloserUtil.close(contentInputStream);
                    }
                }
                if (this.beaconDatabase != null && !foundInBdb) {
                    StoredResponse response = new StoredResponse();
                    response.timeStamp = System.currentTimeMillis();
                    response.foundIn = foundIn;
                }
                // 17&pos=41244981&=G&ref=GRCh37")
                newInfo.addAll(foundIn.stream().map(S -> alt.getDisplayString() + "|" + S).collect(Collectors.toSet()));
            }
            if (newInfo.isEmpty()) {
                out.add(ctx);
                continue;
            }
            final VariantContextBuilder vcb = new VariantContextBuilder(ctx);
            vcb.attribute(infoHeaderLine.getID(), new ArrayList<String>(newInfo));
            out.add(vcb.make());
        }
        return 0;
    } catch (final Exception err) {
        LOG.error(err);
        return -1;
    } finally {
        CloserUtil.close(httpClient);
    }
}