Пример #1
0
 @Test(dataProvider = "failingIntervals")
 public void testDiagnosticLiftover(final Interval fromInterval) {
   final List<LiftOver.PartialLiftover> partials = liftOver.diagnosticLiftover(fromInterval);
   System.out.println("Diagnosing " + fromInterval + " (len " + fromInterval.length() + ")");
   for (final LiftOver.PartialLiftover partial : partials) {
     System.out.println(partial);
   }
 }
Пример #2
0
  @Override
  protected Object doWork() {
    IOUtil.assertFileIsReadable(INPUT);
    IOUtil.assertFileIsReadable(REFERENCE_SEQUENCE);
    IOUtil.assertFileIsReadable(CHAIN);
    IOUtil.assertFileIsWritable(OUTPUT);
    IOUtil.assertFileIsWritable(REJECT);

    ////////////////////////////////////////////////////////////////////////
    // Setup the inputs
    ////////////////////////////////////////////////////////////////////////
    final LiftOver liftOver = new LiftOver(CHAIN);
    final VCFFileReader in = new VCFFileReader(INPUT, false);

    logger.info("Loading up the target reference genome.");
    final ReferenceSequenceFileWalker walker = new ReferenceSequenceFileWalker(REFERENCE_SEQUENCE);
    final Map<String, byte[]> refSeqs = new HashMap<>();
    for (final SAMSequenceRecord rec : walker.getSequenceDictionary().getSequences()) {
      refSeqs.put(rec.getSequenceName(), walker.get(rec.getSequenceIndex()).getBases());
    }
    CloserUtil.close(walker);

    ////////////////////////////////////////////////////////////////////////
    // Setup the outputs
    ////////////////////////////////////////////////////////////////////////
    final VCFHeader inHeader = in.getFileHeader();
    final VCFHeader outHeader = new VCFHeader(inHeader);
    outHeader.setSequenceDictionary(walker.getSequenceDictionary());
    final VariantContextWriter out =
        new VariantContextWriterBuilder()
            .setOption(Options.INDEX_ON_THE_FLY)
            .setOutputFile(OUTPUT)
            .setReferenceDictionary(walker.getSequenceDictionary())
            .build();
    out.writeHeader(outHeader);

    final VariantContextWriter rejects =
        new VariantContextWriterBuilder()
            .setOutputFile(REJECT)
            .unsetOption(Options.INDEX_ON_THE_FLY)
            .build();
    final VCFHeader rejectHeader = new VCFHeader(in.getFileHeader());
    for (final VCFFilterHeaderLine line : FILTERS) rejectHeader.addMetaDataLine(line);
    rejects.writeHeader(rejectHeader);

    ////////////////////////////////////////////////////////////////////////
    // Read the input VCF, lift the records over and write to the sorting
    // collection.
    ////////////////////////////////////////////////////////////////////////
    long failedLiftover = 0, failedAlleleCheck = 0, total = 0;
    logger.info("Lifting variants over and sorting.");

    final SortingCollection<VariantContext> sorter =
        SortingCollection.newInstance(
            VariantContext.class,
            new VCFRecordCodec(outHeader),
            outHeader.getVCFRecordComparator(),
            MAX_RECORDS_IN_RAM,
            TMP_DIR);

    ProgressLogger progress = new ProgressLogger(logger, 1000000, "read");

    for (final VariantContext ctx : in) {
      ++total;
      final Interval source =
          new Interval(
              ctx.getContig(),
              ctx.getStart(),
              ctx.getEnd(),
              false,
              ctx.getContig() + ":" + ctx.getStart() + "-" + ctx.getEnd());
      final Interval target = liftOver.liftOver(source, 1.0);

      if (target == null) {
        rejects.add(new VariantContextBuilder(ctx).filter(FILTER_CANNOT_LIFTOVER).make());
        failedLiftover++;
      } else {
        // Fix the alleles if we went from positive to negative strand
        final List<Allele> alleles = new ArrayList<>();
        for (final Allele oldAllele : ctx.getAlleles()) {
          if (target.isPositiveStrand() || oldAllele.isSymbolic()) {
            alleles.add(oldAllele);
          } else {
            alleles.add(
                Allele.create(
                    SequenceUtil.reverseComplement(oldAllele.getBaseString()),
                    oldAllele.isReference()));
          }
        }

        // Build the new variant context
        final VariantContextBuilder builder =
            new VariantContextBuilder(
                ctx.getSource(), target.getContig(), target.getStart(), target.getEnd(), alleles);

        builder.id(ctx.getID());
        builder.attributes(ctx.getAttributes());
        builder.genotypes(ctx.getGenotypes());
        builder.filters(ctx.getFilters());
        builder.log10PError(ctx.getLog10PError());

        // Check that the reference allele still agrees with the reference sequence
        boolean mismatchesReference = false;
        for (final Allele allele : builder.getAlleles()) {
          if (allele.isReference()) {
            final byte[] ref = refSeqs.get(target.getContig());
            final String refString =
                StringUtil.bytesToString(ref, target.getStart() - 1, target.length());

            if (!refString.equalsIgnoreCase(allele.getBaseString())) {
              mismatchesReference = true;
            }

            break;
          }
        }

        if (mismatchesReference) {
          rejects.add(new VariantContextBuilder(ctx).filter(FILTER_MISMATCHING_REF_ALLELE).make());
          failedAlleleCheck++;
        } else {
          sorter.add(builder.make());
        }
      }

      progress.record(ctx.getContig(), ctx.getStart());
    }

    final NumberFormat pfmt = new DecimalFormat("0.0000%");
    final String pct = pfmt.format((failedLiftover + failedAlleleCheck) / (double) total);
    logger.info("Processed ", total, " variants.");
    logger.info(Long.toString(failedLiftover), " variants failed to liftover.");
    logger.info(
        Long.toString(failedAlleleCheck),
        " variants lifted over but had mismatching reference alleles after lift over.");
    logger.info(pct, " of variants were not successfully lifted over and written to the output.");

    rejects.close();
    in.close();

    ////////////////////////////////////////////////////////////////////////
    // Write the sorted outputs to the final output file
    ////////////////////////////////////////////////////////////////////////
    sorter.doneAdding();
    progress = new ProgressLogger(logger, 1000000, "written");
    logger.info("Writing out sorted records to final VCF.");

    for (final VariantContext ctx : sorter) {
      out.add(ctx);
      progress.record(ctx.getContig(), ctx.getStart());
    }
    out.close();
    sorter.cleanup();

    return null;
  }