Examples with VcfTools com.github.lindenb.jvarkit.util.vcf.VcfTools used on opensource projects

Example 1 with VcfTools

use of com.github.lindenb.jvarkit.util.vcf.VcfTools in project jvarkit by lindenb.

the class VcfGeneEpistasis method doWork.

@Override
public int doWork(final List<String> args) {
    if (this.geneBed == null) {
        LOG.error("gene file bed undefined");
        return -1;
    }
    if (this.outputFile == null) {
        LOG.error("output file undefined");
        return -1;
    }
    CloseableIterator<VariantContext> iter = null;
    try {
        final File vcfFile = new File(oneAndOnlyOneFile(args));
        this.vcfFileReader = new VCFFileReader(vcfFile, true);
        final VCFHeader header = this.vcfFileReader.getFileHeader();
        final Pedigree pedigree;
        if (this.pedigreeFile != null) {
            pedigree = new Pedigree.Parser().parse(this.pedigreeFile);
        } else {
            pedigree = new Pedigree.Parser().parse(header);
        }
        if (pedigree == null || pedigree.isEmpty() || !pedigree.hasAffected() || !pedigree.hasUnaffected()) {
            LOG.error("empty ped or no case/ctrl");
            return -1;
        }
        pedigree.verifyPersonsHaveUniqueNames();
        for (final Pedigree.Person p : pedigree.getPersons().stream().filter(P -> P.isAffected() || P.isUnaffected()).filter(P -> header.getSampleNamesInOrder().contains(P.getId())).collect(Collectors.toSet())) {
            this.id2samples.put(p.getId(), p);
        }
        this.vcfTools = new VcfTools(header);
        List<Interval> geneList;
        if (!this.geneBed.exists()) {
            final Map<String, Interval> gene2interval = new HashMap<>(50000);
            LOG.info("building gene file" + this.geneBed);
            iter = this.vcfFileReader.iterator();
            // iter = this.vcfFileReader.query("chr3",1,300_000_000);
            final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(header).logger(LOG);
            while (iter.hasNext()) {
                final VariantContext ctx = progress.watch(iter.next());
                if (!accept(ctx))
                    continue;
                for (final String geneName : getGenes(ctx)) {
                    final Interval old = gene2interval.get(geneName);
                    if (old == null) {
                        gene2interval.put(geneName, new Interval(ctx.getContig(), ctx.getStart(), ctx.getEnd(), false, geneName));
                        LOG.info("adding " + geneName + ". number of genes: " + gene2interval.size());
                    } else if (!old.getContig().equals(ctx.getContig())) {
                        LOG.error("boum :" + geneName + ": on chrom " + ctx.getContig() + " vs " + old);
                        return -1;
                    } else {
                        gene2interval.put(geneName, new Interval(ctx.getContig(), Math.min(ctx.getStart(), old.getStart()), Math.max(ctx.getEnd(), old.getEnd()), false, geneName));
                    }
                }
            }
            iter.close();
            iter = null;
            progress.finish();
            geneList = new ArrayList<>(gene2interval.values());
            PrintWriter pw = new PrintWriter(this.geneBed);
            for (final Interval g : geneList) {
                pw.println(g.getContig() + "\t" + (g.getStart() - 1) + "\t" + (g.getEnd()) + "\t" + g.getName());
            }
            pw.flush();
            pw.close();
            pw = null;
        } else {
            BedLineCodec codec = new BedLineCodec();
            BufferedReader r = IOUtil.openFileForBufferedReading(geneBed);
            geneList = r.lines().map(L -> codec.decode(L)).filter(B -> B != null).map(B -> new Interval(B.getContig(), B.getStart(), B.getEnd(), true, B.get(3))).collect(Collectors.toList());
            r.close();
        }
        if (geneList.isEmpty()) {
            LOG.error("gene List is empty");
            return -1;
        }
        final Comparator<VariantContext> ctxSorter = VCFUtils.createTidPosRefComparator(header.getSequenceDictionary());
        final Function<Interval, List<VariantContext>> loadVariants = (R) -> {
            List<VariantContext> L = new ArrayList<>();
            CloseableIterator<VariantContext> r = this.vcfFileReader.query(R.getContig(), R.getStart(), R.getEnd());
            while (r.hasNext()) {
                final VariantContext ctx = r.next();
                if (!accept(ctx))
                    continue;
                if (!getGenes(ctx).contains(R.getName()))
                    continue;
                L.add(ctx);
            }
            r.close();
            return L;
        };
        final SkatExecutor executor = this.skatFactory.build();
        Double bestSkat = null;
        LOG.info("number of genes : " + geneList.size());
        final int list_end_index = (this.user_end_index < 0 ? geneList.size() : Math.min(geneList.size(), this.user_end_index));
        for (int x = this.user_begin_index; x < list_end_index; ++x) {
            final Interval intervalx = geneList.get(x);
            final List<VariantContext> variantsx = loadVariants.apply(intervalx);
            if (variantsx.isEmpty())
                continue;
            for (int y = x; y < geneList.size(); /* pas list_end_index */
            ++y) {
                final Interval intervaly;
                final List<VariantContext> merge;
                if (y == x) {
                    // we-re testing gene 1 only
                    intervaly = intervalx;
                    merge = variantsx;
                } else {
                    intervaly = geneList.get(y);
                    if (intervaly.intersects(intervalx))
                        continue;
                    final List<VariantContext> variantsy = loadVariants.apply(intervaly);
                    if (variantsy.isEmpty())
                        continue;
                    merge = new MergedList<>(variantsx, variantsy);
                }
                LOG.info("testing : [" + x + "]" + intervalx + " [" + y + "]" + intervaly + " N:" + geneList.size() + " best: " + bestSkat);
                final Double skat = eval(executor, merge);
                if (skat == null)
                    continue;
                if (bestSkat == null || skat.compareTo(bestSkat) < 0) {
                    bestSkat = skat;
                    LOG.info("best " + bestSkat + " " + intervalx + " " + intervaly);
                    if (this.outputFile.getName().endsWith(".vcf") || this.outputFile.getName().endsWith(".vcf.gz")) {
                        final VCFHeader header2 = new VCFHeader(header);
                        header2.addMetaDataLine(new VCFHeaderLine(VcfGeneEpistasis.class.getName(), intervalx.getName() + " " + intervaly.getName() + " " + bestSkat));
                        final VariantContextWriter w = VCFUtils.createVariantContextWriter(outputFile);
                        w.writeHeader(header2);
                        merge.stream().sorted(ctxSorter).forEach(V -> w.add(V));
                        w.close();
                    } else {
                        final PrintWriter w = super.openFileOrStdoutAsPrintWriter(outputFile);
                        w.println(String.valueOf(bestSkat) + "\t" + intervalx.getName() + "\t" + intervaly.getName());
                        w.flush();
                        w.close();
                    }
                }
            }
        }
        return 0;
    } catch (final Exception err) {
        LOG.error(err);
        return -1;
    } finally {
        CloserUtil.close(iter);
        CloserUtil.close(this.vcfFileReader);
    }
}

Example 2 with VcfTools

use of com.github.lindenb.jvarkit.util.vcf.VcfTools in project jvarkit by lindenb.

the class GroupByGene method read.

private void read(final String input) throws IOException {
    LineIterator lineiter = null;
    SortingCollection<Call> sortingCollection = null;
    try {
        final Pattern regexType = (StringUtil.isBlank(this.typeRegexExclude) ? null : Pattern.compile(this.typeRegexExclude));
        lineiter = (input == null ? IOUtils.openStreamForLineIterator(stdin()) : IOUtils.openURIForLineIterator(input));
        sortingCollection = SortingCollection.newInstance(Call.class, new CallCodec(), (C1, C2) -> {
            int i = C1.compareTo(C2);
            if (i != 0)
                return i;
            return C1.line.compareTo(C2.line);
        }, this.writingSortingCollection.getMaxRecordsInRam(), this.writingSortingCollection.getTmpPaths());
        sortingCollection.setDestructiveIteration(true);
        final VCFUtils.CodecAndHeader cah = VCFUtils.parseHeader(lineiter);
        final VCFHeader header = cah.header;
        this.the_dictionary = header.getSequenceDictionary();
        if (this.the_dictionary == null || this.the_dictionary.isEmpty()) {
            throw new JvarkitException.DictionaryMissing(input);
        }
        this.the_codec = cah.codec;
        final List<String> sampleNames;
        if (header.getSampleNamesInOrder() != null) {
            sampleNames = header.getSampleNamesInOrder();
        } else {
            sampleNames = Collections.emptyList();
        }
        final VcfTools vcfTools = new VcfTools(header);
        final Pedigree pedigree;
        if (this.pedigreeFile != null) {
            pedigree = Pedigree.newParser().parse(this.pedigreeFile);
        } else {
            pedigree = Pedigree.newParser().parse(header);
        }
        final Pattern tab = Pattern.compile("[\t]");
        final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(the_dictionary).logger(LOG);
        while (lineiter.hasNext()) {
            String line = lineiter.next();
            final VariantContext ctx = progress.watch(this.the_codec.decode(line));
            if (!ctx.isVariant())
                continue;
            if (ignore_filtered && ctx.isFiltered())
                continue;
            // simplify line
            final String[] tokens = tab.split(line);
            // ID
            tokens[2] = VCFConstants.EMPTY_ID_FIELD;
            // QUAL
            tokens[5] = VCFConstants.MISSING_VALUE_v4;
            // FILTER
            tokens[6] = VCFConstants.UNFILTERED;
            // INFO
            tokens[7] = VCFConstants.EMPTY_INFO_FIELD;
            line = String.join(VCFConstants.FIELD_SEPARATOR, Arrays.asList(tokens));
            for (final GeneName g : getGenes(vcfTools, ctx)) {
                if (regexType != null && regexType.matcher(g.type).matches())
                    continue;
                final Call c = new Call();
                c.line = line;
                c.gene = g;
                sortingCollection.add(c);
            }
        }
        CloserUtil.close(lineiter);
        lineiter = null;
        sortingCollection.doneAdding();
        /**
         * dump
         */
        final Set<String> casesSamples = pedigree.getPersons().stream().filter(P -> P.isAffected()).map(P -> P.getId()).filter(ID -> sampleNames.contains(ID)).collect(Collectors.toSet());
        final Set<String> controlsSamples = pedigree.getPersons().stream().filter(P -> P.isUnaffected()).map(P -> P.getId()).filter(ID -> sampleNames.contains(ID)).collect(Collectors.toSet());
        final Set<String> maleSamples = pedigree.getPersons().stream().filter(P -> P.isMale()).map(P -> P.getId()).filter(ID -> sampleNames.contains(ID)).collect(Collectors.toSet());
        final Set<String> femaleSamples = pedigree.getPersons().stream().filter(P -> P.isFemale()).map(P -> P.getId()).filter(ID -> sampleNames.contains(ID)).collect(Collectors.toSet());
        final Predicate<Genotype> genotypeFilter = genotype -> {
            if (!genotype.isAvailable())
                return false;
            if (!genotype.isCalled())
                return false;
            if (genotype.isNoCall())
                return false;
            if (genotype.isHomRef())
                return false;
            if (this.ignore_filtered_genotype && genotype.isFiltered())
                return false;
            return true;
        };
        PrintStream pw = openFileOrStdoutAsPrintStream(this.outFile);
        pw.print("#chrom");
        pw.print('\t');
        pw.print("min.POS");
        pw.print('\t');
        pw.print("max.POS");
        pw.print('\t');
        pw.print("gene.name");
        pw.print('\t');
        pw.print("gene.type");
        pw.print('\t');
        pw.print("samples.affected");
        pw.print('\t');
        pw.print("count.variations");
        if (!casesSamples.isEmpty()) {
            pw.print('\t');
            pw.print("pedigree.cases");
        }
        if (!controlsSamples.isEmpty()) {
            pw.print('\t');
            pw.print("pedigree.controls");
        }
        if (!maleSamples.isEmpty()) {
            pw.print('\t');
            pw.print("pedigree.males");
        }
        if (!femaleSamples.isEmpty()) {
            pw.print('\t');
            pw.print("pedigree.females");
        }
        if (this.print_fisher && !controlsSamples.isEmpty() && !casesSamples.isEmpty()) {
            pw.print('\t');
            pw.print("fisher");
        }
        for (final String sample : sampleNames) {
            pw.print('\t');
            pw.print(sample);
        }
        pw.println();
        final CloseableIterator<Call> iter = sortingCollection.iterator();
        final EqualRangeIterator<Call> eqiter = new EqualRangeIterator<>(iter, (C1, C2) -> C1.compareTo(C2));
        while (eqiter.hasNext()) {
            final List<Call> row = eqiter.next();
            final Call first = row.get(0);
            final List<VariantContext> variantList = row.stream().map(R -> GroupByGene.this.the_codec.decode(R.line)).collect(Collectors.toList());
            final int minPos = variantList.stream().mapToInt(R -> R.getStart()).min().getAsInt();
            final int maxPos = variantList.stream().mapToInt(R -> R.getEnd()).max().getAsInt();
            final Set<String> sampleCarryingMut = new HashSet<String>();
            final Counter<String> pedCasesCarryingMut = new Counter<String>();
            final Counter<String> pedCtrlsCarryingMut = new Counter<String>();
            final Counter<String> malesCarryingMut = new Counter<String>();
            final Counter<String> femalesCarryingMut = new Counter<String>();
            final Counter<String> sample2count = new Counter<String>();
            for (final VariantContext ctx : variantList) {
                for (final Genotype genotype : ctx.getGenotypes()) {
                    if (!genotypeFilter.test(genotype))
                        continue;
                    final String sampleName = genotype.getSampleName();
                    sample2count.incr(sampleName);
                    sampleCarryingMut.add(sampleName);
                    if (casesSamples.contains(sampleName)) {
                        pedCasesCarryingMut.incr(sampleName);
                    }
                    if (controlsSamples.contains(sampleName)) {
                        pedCtrlsCarryingMut.incr(sampleName);
                    }
                    if (maleSamples.contains(sampleName)) {
                        malesCarryingMut.incr(sampleName);
                    }
                    if (femaleSamples.contains(sampleName)) {
                        femalesCarryingMut.incr(sampleName);
                    }
                }
            }
            pw.print(first.getContig());
            pw.print('\t');
            // convert to bed
            pw.print(minPos - 1);
            pw.print('\t');
            pw.print(maxPos);
            pw.print('\t');
            pw.print(first.gene.name);
            pw.print('\t');
            pw.print(first.gene.type);
            pw.print('\t');
            pw.print(sampleCarryingMut.size());
            pw.print('\t');
            pw.print(variantList.size());
            if (!casesSamples.isEmpty()) {
                pw.print('\t');
                pw.print(pedCasesCarryingMut.getCountCategories());
            }
            if (!controlsSamples.isEmpty()) {
                pw.print('\t');
                pw.print(pedCtrlsCarryingMut.getCountCategories());
            }
            if (!maleSamples.isEmpty()) {
                pw.print('\t');
                pw.print(malesCarryingMut.getCountCategories());
            }
            if (!femaleSamples.isEmpty()) {
                pw.print('\t');
                pw.print(femalesCarryingMut.getCountCategories());
            }
            if (this.print_fisher && !controlsSamples.isEmpty() && !casesSamples.isEmpty()) {
                int count_case_mut = 0;
                int count_ctrl_mut = 0;
                int count_case_wild = 0;
                int count_ctrl_wild = 0;
                for (final VariantContext ctx : variantList) {
                    for (final Genotype genotype : ctx.getGenotypes()) {
                        final String sampleName = genotype.getSampleName();
                        final boolean has_mutation = genotypeFilter.test(genotype);
                        if (controlsSamples.contains(sampleName)) {
                            if (has_mutation) {
                                count_ctrl_mut++;
                            } else {
                                count_ctrl_wild++;
                            }
                        } else if (casesSamples.contains(sampleName)) {
                            if (has_mutation) {
                                count_case_mut++;
                            } else {
                                count_case_wild++;
                            }
                        }
                    }
                }
                final FisherExactTest fisher = FisherExactTest.compute(count_case_mut, count_case_wild, count_ctrl_mut, count_ctrl_wild);
                pw.print('\t');
                pw.print(fisher.getAsDouble());
            }
            for (final String sample : sampleNames) {
                pw.print('\t');
                pw.print(sample2count.count(sample));
            }
            pw.println();
            if (pw.checkError())
                break;
        }
        eqiter.close();
        iter.close();
        pw.flush();
        if (this.outFile != null)
            pw.close();
    } finally {
        CloserUtil.close(lineiter);
        if (sortingCollection != null)
            sortingCollection.cleanup();
    }
}

Example 3 with VcfTools

use of com.github.lindenb.jvarkit.util.vcf.VcfTools in project jvarkit by lindenb.

the class VCFFilterJS method doVcfToVcf.

@Override
protected int doVcfToVcf(final String inputName, final VcfIterator r, final VariantContextWriter w) {
    try {
        final VCFHeader header = r.getHeader();
        final VcfTools vcfTools = new VcfTools(header);
        final VCFHeader h2 = new VCFHeader(header);
        addMetaData(h2);
        final Pedigree pedigree;
        if (pedigreeFile != null) {
            pedigree = Pedigree.newParser().parse(this.pedigreeFile);
        } else // try to read from VCF header
        {
            Pedigree p = null;
            try {
                p = Pedigree.newParser().parse(header);
            } catch (final Exception err) {
                LOG.warn("cannot decode pedigree from vcf header");
                p = Pedigree.createEmptyPedigree();
            }
            pedigree = p;
        }
        final VCFFilterHeaderLine filterHeaderLine = (filteredTag.trim().isEmpty() ? null : new VCFFilterHeaderLine(this.filteredTag.trim(), "Filtered with " + getProgramName()));
        if (filterHeaderLine != null)
            h2.addMetaDataLine(filterHeaderLine);
        final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(header).logger(LOG);
        final Bindings bindings = this.compiledScript.getEngine().createBindings();
        bindings.put("header", header);
        bindings.put("tools", vcfTools);
        bindings.put("pedigree", pedigree);
        bindings.put("individuals", Collections.unmodifiableList(pedigree.getPersons().stream().filter(P -> (P.isAffected() || P.isUnaffected())).filter(P -> P.hasUniqId()).filter(P -> header.getSampleNamesInOrder().contains(P.getId())).collect(Collectors.toList())));
        for (final String jsonkv : this.jsonFiles) {
            int eq = jsonkv.indexOf("=");
            if (eq <= 0)
                throw new JvarkitException.UserError("Bad format for json . expected key=/path/to/file.json but got '" + jsonkv + "'");
            final String key = jsonkv.substring(0, eq);
            final FileReader jsonFile = new FileReader(jsonkv.substring(eq + 1));
            JsonParser jsonParser = new JsonParser();
            final JsonElement root = jsonParser.parse(jsonFile);
            jsonFile.close();
            bindings.put(key, root);
        }
        w.writeHeader(h2);
        while (r.hasNext() && !w.checkError()) {
            final VariantContext variation = progress.watch(r.next());
            bindings.put("variant", variation);
            final Object result = compiledScript.eval(bindings);
            // result is an array of a collection of variants
            if (result != null && (result.getClass().isArray() || (result instanceof Collection))) {
                final Collection<?> col;
                if (result.getClass().isArray()) {
                    final Object[] array = (Object[]) result;
                    col = Arrays.asList(array);
                } else {
                    col = (Collection<?>) result;
                }
                // write all of variants
                for (final Object item : col) {
                    if (item == null)
                        throw new JvarkitException.UserError("item in array is null");
                    if (!(item instanceof VariantContext))
                        throw new JvarkitException.UserError("item in array is not a VariantContext " + item.getClass());
                    w.add(VariantContext.class.cast(item));
                }
            } else // result is a VariantContext
            if (result != null && (result instanceof VariantContext)) {
                w.add(VariantContext.class.cast(result));
            } else {
                boolean accept = true;
                if (result == null) {
                    accept = false;
                } else if (result instanceof Boolean) {
                    if (Boolean.FALSE.equals(result))
                        accept = false;
                } else if (result instanceof Number) {
                    if (((Number) result).intValue() != 1)
                        accept = false;
                } else {
                    LOG.warn("Script returned something that is not a boolean or a number:" + result.getClass());
                    accept = false;
                }
                if (!accept) {
                    if (filterHeaderLine != null) {
                        final VariantContextBuilder vcb = new VariantContextBuilder(variation);
                        vcb.filter(filterHeaderLine.getID());
                        w.add(vcb.make());
                    }
                    continue;
                }
                // set PASS filter if needed
                if (filterHeaderLine != null && !variation.isFiltered()) {
                    w.add(new VariantContextBuilder(variation).passFilters().make());
                    continue;
                }
                w.add(variation);
            }
        }
        return RETURN_OK;
    } catch (final Exception err) {
        LOG.error(err);
        return -1;
    } finally {
    }
}

Example 4 with VcfTools

use of com.github.lindenb.jvarkit.util.vcf.VcfTools in project jvarkit by lindenb.

the class KnimeVariantHelper method forEachVariantData.

public Stream<VariantData> forEachVariantData(final String vcfFile) throws IOException {
    final File file = new File(vcfFile);
    IOUtil.assertFileIsReadable(file);
    final VCFFileReader r = new VCFFileReader(file, false);
    final VCFHeader header = r.getFileHeader();
    this.init(header);
    final VcfTools vcfTools = new VcfTools(header);
    final CloseableIterator<VariantContext> iter = r.iterator();
    final Iterable<VariantContext> iterable = () -> iter;
    return StreamSupport.stream(iterable.spliterator(), false).onClose(() -> {
        CloserUtil.close(iter);
        CloserUtil.close(r);
    }).map(V -> new VariantData(V) {

        @Override
        public VCFHeader getVcfHeader() {
            return header;
        }

        @Override
        public VcfTools getVcfTools() {
            return vcfTools;
        }
    });
}

Example 5 with VcfTools

use of com.github.lindenb.jvarkit.util.vcf.VcfTools in project jvarkit by lindenb.

the class VcfLoopOverGenes method doWork.

@SuppressWarnings("resource")
@Override
public int doWork(final List<String> args) {
    PrintWriter pw = null;
    VCFFileReader vcfFileReader = null;
    CloseableIterator<VariantContext> iter = null;
    CloseableIterator<GeneLoc> iter2 = null;
    BufferedReader br = null;
    ArchiveFactory archive = null;
    try {
        final File vcf = new File(oneAndOnlyOneFile(args));
        vcfFileReader = new VCFFileReader(vcf, (this.geneFile != null || !StringUtil.isBlank(this.regionStr)));
        this.dictionary = vcfFileReader.getFileHeader().getSequenceDictionary();
        if (this.dictionary == null) {
            throw new JvarkitException.VcfDictionaryMissing(vcf);
        }
        final VcfTools tools = new VcfTools(vcfFileReader.getFileHeader());
        if (!this.prefix.isEmpty() && !this.prefix.endsWith(".")) {
            this.prefix += ".";
        }
        if (this.geneFile == null) {
            final SortingCollection<GeneLoc> sortingCollection = SortingCollection.newInstance(GeneLoc.class, new GeneLocCodec(), (A, B) -> A.compareTo(B), this.writingSortingCollection.getMaxRecordsInRam(), this.writingSortingCollection.getTmpPaths());
            sortingCollection.setDestructiveIteration(true);
            if (StringUtil.isBlank(this.regionStr)) {
                iter = vcfFileReader.iterator();
            } else {
                final IntervalParser parser = new IntervalParser(this.dictionary);
                parser.setContigNameIsWholeContig(true);
                final Interval interval = parser.parse(this.regionStr);
                if (interval == null) {
                    LOG.error("Cannot parse interval " + this.regionStr);
                    return -1;
                }
                iter = vcfFileReader.query(interval.getContig(), interval.getStart(), interval.getEnd());
            }
            final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(vcfFileReader.getFileHeader()).logger(LOG);
            if (this.splitMethod.equals(SplitMethod.Annotations)) {
                while (iter.hasNext()) {
                    final VariantContext ctx = progress.watch(iter.next());
                    for (final AnnPredictionParser.AnnPrediction pred : tools.getAnnPredictionParser().getPredictions(ctx)) {
                        if (this.snpEffNoIntergenic && pred.isIntergenicRegion()) {
                            continue;
                        }
                        if (!StringUtil.isBlank(pred.getGeneName())) {
                            sortingCollection.add(create(ctx, pred.getGeneName(), SourceType.ANN_GeneName));
                        }
                        if (!StringUtil.isBlank(pred.getGeneId())) {
                            sortingCollection.add(create(ctx, pred.getGeneId(), SourceType.ANN_GeneID));
                        }
                        if (!StringUtil.isBlank(pred.getFeatureId())) {
                            sortingCollection.add(create(ctx, pred.getFeatureId(), SourceType.ANN_FeatureID));
                        }
                    }
                    for (final VepPredictionParser.VepPrediction pred : tools.getVepPredictionParser().getPredictions(ctx)) {
                        if (!StringUtil.isBlank(pred.getGene())) {
                            sortingCollection.add(create(ctx, pred.getGene(), SourceType.VEP_Gene));
                        }
                        if (!StringUtil.isBlank(pred.getFeature())) {
                            sortingCollection.add(create(ctx, pred.getFeature(), SourceType.VEP_Feature));
                        }
                        if (!StringUtil.isBlank(pred.getSymbol())) {
                            sortingCollection.add(create(ctx, pred.getSymbol(), SourceType.VEP_Symbol));
                        }
                        if (!StringUtil.isBlank(pred.getHgncId())) {
                            sortingCollection.add(create(ctx, pred.getHgncId(), SourceType.VEP_HgncId));
                        }
                    }
                }
            } else /**
             * split VCF per sliding window of variants
             */
            if (this.splitMethod.equals(SplitMethod.VariantSlidingWindow)) {
                if (this.variantsWinCount < 1) {
                    LOG.error("Bad value for variantsWinCount");
                    return -1;
                }
                if (this.variantsWinShift < 1 || this.variantsWinShift > this.variantsWinCount) {
                    LOG.error("Bad value for variantsWinShift");
                    return -1;
                }
                final List<VariantContext> buffer = new ArrayList<>(this.variantsWinCount);
                /**
                 * routine to dump buffer into sorting collection
                 */
                final Runnable dumpBuffer = () -> {
                    if (buffer.isEmpty())
                        return;
                    final String contig = buffer.get(0).getContig();
                    final int chromStart = buffer.stream().mapToInt(CTX -> CTX.getStart()).min().getAsInt();
                    // use last of start too
                    final int chromEnd0 = buffer.stream().mapToInt(CTX -> CTX.getStart()).max().getAsInt();
                    // final int chromEnd1 = buffer.stream().mapToInt(CTX->CTX.getEnd()).max().getAsInt();
                    final String identifier = contig + "_" + String.format(NUM_FORMAT, chromStart) + "_" + String.format(NUM_FORMAT, chromEnd0);
                    for (final VariantContext ctx : buffer) {
                        sortingCollection.add(create(ctx, identifier, SourceType.SlidingVariants));
                    }
                };
                while (iter.hasNext()) {
                    VariantContext ctx = progress.watch(iter.next());
                    /* reduce the memory footprint for this context */
                    ctx = new VariantContextBuilder(ctx).genotypes(Collections.emptyList()).unfiltered().rmAttributes(new ArrayList<>(ctx.getAttributes().keySet())).make();
                    if (!buffer.isEmpty() && !buffer.get(0).getContig().equals(ctx.getContig())) {
                        dumpBuffer.run();
                        buffer.clear();
                    }
                    buffer.add(ctx);
                    if (buffer.size() >= this.variantsWinCount) {
                        dumpBuffer.run();
                        final int fromIndex = Math.min(this.variantsWinShift, buffer.size());
                        buffer.subList(0, fromIndex).clear();
                    }
                }
                dumpBuffer.run();
                buffer.clear();
            } else if (this.splitMethod.equals(SplitMethod.ContigSlidingWindow)) {
                if (this.contigWinLength < 1) {
                    LOG.error("Bad value for contigWinCount");
                    return -1;
                }
                if (this.contigWinShift < 1 || this.contigWinShift > this.contigWinLength) {
                    LOG.error("Bad value for contigWinShift");
                    return -1;
                }
                while (iter.hasNext()) {
                    VariantContext ctx = progress.watch(iter.next());
                    /* reduce the memory footprint for this context */
                    ctx = new VariantContextBuilder(ctx).genotypes(Collections.emptyList()).unfiltered().rmAttributes(new ArrayList<>(ctx.getAttributes().keySet())).make();
                    int start = 0;
                    while (start <= ctx.getStart()) {
                        if (start + this.contigWinLength >= ctx.getStart()) {
                            final int chromStart = start;
                            final int chromEnd0 = start + this.contigWinLength;
                            final String identifier = ctx.getContig() + "_" + String.format(NUM_FORMAT, chromStart) + "_" + String.format(NUM_FORMAT, chromEnd0);
                            sortingCollection.add(create(ctx, identifier, SourceType.SlidingContig));
                        }
                        start += this.contigWinShift;
                    }
                }
            } else {
                throw new IllegalStateException("No such method: " + this.splitMethod);
            }
            sortingCollection.doneAdding();
            progress.finish();
            iter.close();
            iter = null;
            pw = super.openFileOrStdoutAsPrintWriter(this.outputFile);
            iter2 = sortingCollection.iterator();
            final EqualRangeIterator<GeneLoc> eqiter = new EqualRangeIterator<>(iter2, this.compareGeneName);
            int geneIdentifierId = 0;
            while (eqiter.hasNext()) {
                final List<GeneLoc> gene = eqiter.next();
                pw.print(gene.get(0).contig);
                pw.print('\t');
                // -1 for BED
                pw.print(gene.stream().mapToInt(G -> G.start).min().getAsInt() - 1);
                pw.print('\t');
                pw.print(gene.stream().mapToInt(G -> G.end).max().getAsInt());
                pw.print('\t');
                pw.print(this.prefix + String.format("%09d", ++geneIdentifierId));
                pw.print('\t');
                pw.print(gene.get(0).geneName);
                pw.print('\t');
                pw.print(gene.get(0).sourceType);
                pw.print('\t');
                pw.print(gene.size());
                pw.println();
            }
            pw.flush();
            pw.close();
            pw = null;
            eqiter.close();
            iter2.close();
            iter2 = null;
            sortingCollection.cleanup();
        } else {
            if (this.nJobs < 1) {
                this.nJobs = Math.max(1, Runtime.getRuntime().availableProcessors());
                LOG.info("setting njobs to " + this.nJobs);
            }
            final ExecutorService executorService;
            final List<Future<Integer>> futureResults;
            if (this.nJobs > 1) {
                executorService = new ThreadPoolExecutor(this.nJobs, this.nJobs, 0L, TimeUnit.MILLISECONDS, new LinkedBlockingQueue<Runnable>());
                futureResults = new ArrayList<>();
            } else {
                executorService = null;
                futureResults = Collections.emptyList();
            }
            if (this.outputFile == null) {
                LOG.error("When scanning a VCF with " + this.geneFile + ". Output file must be defined");
            }
            if (!this.exec.isEmpty()) {
                if (this.outputFile.getName().endsWith(".zip")) {
                    LOG.error("Cannot execute " + this.exec + " when saving to a zip.");
                    return -1;
                }
            }
            archive = ArchiveFactory.open(this.outputFile);
            PrintWriter manifest = this.deleteAfterCommand && !this.exec.isEmpty() ? // all files will be deleted, no manifest needed
            new PrintWriter(new NullOuputStream()) : archive.openWriter(this.prefix + "manifest.txt");
            br = IOUtils.openFileForBufferedReading(this.geneFile);
            final BedLineCodec bedCodec = new BedLineCodec();
            for (; ; ) {
                if (!futureResults.isEmpty()) {
                    int i = 0;
                    while (i < futureResults.size()) {
                        final Future<Integer> r = futureResults.get(i);
                        if (r.isCancelled()) {
                            LOG.error("Task was canceled. Break.");
                            return -1;
                        } else if (r.isDone()) {
                            futureResults.remove(i);
                            int rez = r.get();
                            if (rez != 0) {
                                LOG.error("Task Failed (" + rez + "). Break");
                            }
                        } else {
                            i++;
                        }
                    }
                }
                final String line = br.readLine();
                if (line == null)
                    break;
                if (line.startsWith("#") || line.isEmpty())
                    continue;
                final BedLine bedLine = bedCodec.decode(line);
                if (bedLine == null)
                    continue;
                // ID
                final String geneIdentifier = bedLine.get(3);
                // name
                final String geneName = bedLine.get(4);
                final SourceType sourceType = SourceType.valueOf(bedLine.get(5));
                final String filename = geneIdentifier;
                final String outputVcfName = (filename.startsWith(this.prefix) ? "" : this.prefix) + filename + ".vcf" + (this.compress ? ".gz" : "");
                LOG.info(bedLine.getContig() + ":" + bedLine.getStart() + "-" + bedLine.getEnd() + " length :" + (bedLine.getEnd() - bedLine.getStart()));
                if (bedLine.getEnd() - bedLine.getStart() > 1E6) {
                    LOG.warn("That's a large region ! " + bedLine);
                }
                OutputStream vcfOutputStream = null;
                VariantContextWriter vw = null;
                int countVariants = 0;
                final SAMSequenceDictionaryProgress progress = new SAMSequenceDictionaryProgress(vcfFileReader.getFileHeader()).logger(LOG).prefix(geneName + " " + bedLine.getContig() + ":" + bedLine.getStart() + "-" + bedLine.getEnd());
                iter = vcfFileReader.query(bedLine.getContig(), bedLine.getStart(), bedLine.getEnd());
                while (iter.hasNext()) {
                    VariantContext ctx = progress.watch(iter.next());
                    switch(sourceType) {
                        case SlidingVariants:
                            {
                                // nothing
                                break;
                            }
                        case SlidingContig:
                            {
                                // nothing
                                break;
                            }
                        case ANN_GeneName:
                        case ANN_FeatureID:
                        case ANN_GeneID:
                            {
                                final List<String> preds = new ArrayList<>();
                                for (final AnnPredictionParser.AnnPrediction pred : tools.getAnnPredictionParser().getPredictions(ctx)) {
                                    final String predictionIdentifier;
                                    switch(sourceType) {
                                        case ANN_GeneName:
                                            predictionIdentifier = pred.getGeneName();
                                            break;
                                        case ANN_FeatureID:
                                            predictionIdentifier = pred.getFeatureId();
                                            break;
                                        case ANN_GeneID:
                                            predictionIdentifier = pred.getGeneId();
                                            break;
                                        default:
                                            throw new IllegalStateException(bedLine.toString());
                                    }
                                    if (StringUtil.isBlank(predictionIdentifier))
                                        continue;
                                    if (!geneName.equals(predictionIdentifier))
                                        continue;
                                    preds.add(pred.getOriginalAttributeAsString());
                                }
                                if (preds.isEmpty()) {
                                    ctx = null;
                                } else {
                                    ctx = new VariantContextBuilder(ctx).rmAttribute(tools.getAnnPredictionParser().getTag()).attribute(tools.getAnnPredictionParser().getTag(), preds).make();
                                }
                                break;
                            }
                        case VEP_Gene:
                        case VEP_Feature:
                        case VEP_Symbol:
                        case VEP_HgncId:
                            {
                                final List<String> preds = new ArrayList<>();
                                for (final VepPredictionParser.VepPrediction pred : tools.getVepPredictions(ctx)) {
                                    final String predictionIdentifier;
                                    switch(sourceType) {
                                        case VEP_Gene:
                                            predictionIdentifier = pred.getGene();
                                            break;
                                        case VEP_Feature:
                                            predictionIdentifier = pred.getFeature();
                                            break;
                                        case VEP_Symbol:
                                            predictionIdentifier = pred.getSymbol();
                                            break;
                                        case VEP_HgncId:
                                            predictionIdentifier = pred.getHgncId();
                                            break;
                                        default:
                                            throw new IllegalStateException(bedLine.toString());
                                    }
                                    if (StringUtil.isBlank(predictionIdentifier))
                                        continue;
                                    if (!geneName.equals(predictionIdentifier))
                                        continue;
                                    preds.add(pred.getOriginalAttributeAsString());
                                }
                                if (preds.isEmpty()) {
                                    ctx = null;
                                } else {
                                    ctx = new VariantContextBuilder(ctx).rmAttribute(tools.getVepPredictionParser().getTag()).attribute(tools.getVepPredictionParser().getTag(), preds).make();
                                }
                                break;
                            }
                        default:
                            throw new IllegalStateException(bedLine.toString());
                    }
                    if (ctx == null)
                        continue;
                    if (vcfOutputStream == null) {
                        LOG.info(filename);
                        manifest.println(outputVcfName);
                        final VCFHeader header = new VCFHeader(vcfFileReader.getFileHeader());
                        header.addMetaDataLine(new VCFHeaderLine(VCF_HEADER_SPLITKEY, filename));
                        vcfOutputStream = archive.openOuputStream(outputVcfName);
                        vw = VCFUtils.createVariantContextWriterToOutputStream(vcfOutputStream);
                        vw.writeHeader(header);
                    }
                    countVariants++;
                    vw.add(ctx);
                    if (countVariants % 1000 == 0) {
                        LOG.info("Loading : " + geneIdentifier + " N=" + countVariants);
                    }
                }
                progress.finish();
                LOG.info(geneIdentifier + " N=" + countVariants);
                if (vcfOutputStream != null) {
                    vw.close();
                    vcfOutputStream.flush();
                    vcfOutputStream.close();
                    vw = null;
                    if (!this.exec.isEmpty()) {
                        final Callable<Integer> callable = () -> {
                            final File vcfOutFile = new File(this.outputFile, outputVcfName);
                            IOUtil.assertFileIsReadable(vcfOutFile);
                            final String vcfPath = vcfOutFile.getPath();
                            final StringTokenizer st = new StringTokenizer(this.exec);
                            final List<String> command = new ArrayList<>(1 + st.countTokens());
                            while (st.hasMoreTokens()) {
                                String token = st.nextToken().replaceAll("__PREFIX__", this.prefix).replaceAll("__CONTIG__", bedLine.getContig()).replaceAll("__CHROM__", bedLine.getContig()).replaceAll("__ID__", geneIdentifier).replaceAll("__NAME__", geneName).replaceAll("__START__", String.valueOf(bedLine.getStart())).replaceAll("__END__", String.valueOf(bedLine.getEnd())).replaceAll("__SOURCE__", sourceType.name()).replaceAll("__VCF__", vcfPath);
                                command.add(token);
                            }
                            LOG.info(command.stream().map(S -> "'" + S + "'").collect(Collectors.joining(" ")));
                            final ProcessBuilder pb = new ProcessBuilder(command);
                            pb.redirectErrorStream(true);
                            final Process p = pb.start();
                            final Thread stdoutThread = new Thread(() -> {
                                try {
                                    InputStream in = p.getInputStream();
                                    IOUtils.copyTo(in, stdout());
                                } catch (Exception err) {
                                    LOG.error(err);
                                }
                            });
                            stdoutThread.start();
                            int exitValue = p.waitFor();
                            if (exitValue != 0) {
                                LOG.error("Command failed (" + exitValue + "):" + String.join(" ", command));
                                return -1;
                            } else {
                                if (deleteAfterCommand) {
                                    if (!vcfOutFile.delete()) {
                                        LOG.warn("Cannot delete " + vcfOutFile);
                                    }
                                }
                                return 0;
                            }
                        };
                        if (executorService != null) {
                            final Future<Integer> rez = executorService.submit(callable);
                            futureResults.add(rez);
                        } else {
                            final int ret = callable.call();
                            if (ret != 0) {
                                LOG.error("Error with process (" + ret + ")");
                                return ret;
                            }
                        }
                    }
                } else {
                    manifest.println("#" + filename);
                    LOG.warn("No Variant Found for " + line);
                }
                iter.close();
            }
            ;
            if (executorService != null) {
                LOG.info("shutdown");
                executorService.shutdown();
                executorService.awaitTermination(365, TimeUnit.DAYS);
            }
            br.close();
            br = null;
            manifest.close();
            archive.close();
            archive = null;
            LOG.info("Done");
        }
        vcfFileReader.close();
        vcfFileReader = null;
        return 0;
    } catch (Exception e) {
        LOG.error(e);
        return -1;
    } finally {
        {
            CloserUtil.close(iter2);
            CloserUtil.close(iter);
            CloserUtil.close(pw);
            CloserUtil.close(vcfFileReader);
            CloserUtil.close(br);
            CloserUtil.close(archive);
        }
    }
}