Exemple #1
0
  /**
   * Is this single change a LOF?
   *
   * <p>Criteria: 1) Core splice sites acceptors or donors (only CORE ones) 2) Stop gained (if this
   * happens at the last part of the protein, we assume it has no effect) 3) Frame shifts
   *
   * @param changeEffect
   * @return
   */
  protected boolean isNmd(ChangeEffect changeEffect) {
    Transcript tr = changeEffect.getTranscript();
    if (tr == null)
      throw new RuntimeException("Transcript not found for change:\n\t" + changeEffect);

    // Only one exon? Nothing to do (there is no exon-exon junction)
    if (tr.numChilds() <= 1) return false;

    // Find last valid NMD position
    int lastNmdPos = lastNmdPos(tr);
    if (lastNmdPos < 0) return false; // No valid 'lastNmdPos'? => There is no NMD event.

    // Does this change affect the region 'before' this last NMD position? => It is assumed to be
    // NMD
    Variant seqChange = changeEffect.getSeqChange();

    boolean nmd;
    if (tr.isStrandPlus()) nmd = seqChange.getStart() <= lastNmdPos;
    else nmd = lastNmdPos <= seqChange.getEnd();

    // Update sets and counters
    if (nmd) {
      transcriptsNmd.add(
          changeEffect
              .getTranscript()); // Unique transcripts affected (WARNING: null will be added)
      genesNmd.add(changeEffect.getGene()); // Unique genes affected (WARNING: null will be added)
      nmdCount++;
    }

    return nmd;
  }
Exemple #2
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  /**
   * Is this deletion a LOF?
   *
   * <p>Criteria: 1) First (coding) exon deleted 2) More than 50% of coding sequence deleted
   *
   * @param changeEffect
   * @return
   */
  protected boolean isLofDeletion(ChangeEffect changeEffect) {
    Transcript tr = changeEffect.getTranscript();
    if (tr == null)
      throw new RuntimeException("Transcript not found for change:\n\t" + changeEffect);

    // ---
    // Criteria:
    // 		1) First (coding) exon deleted
    // ---
    if (changeEffect.getEffectType() == EffectType.EXON_DELETED) {
      Variant seqChange = changeEffect.getSeqChange();
      if (seqChange == null)
        throw new RuntimeException("Cannot retrieve 'seqChange' from EXON_DELETED effect!");
      if (seqChange.includes(tr.getFirstCodingExon())) return true;
    }

    // ---
    // Criteria:
    // 		2) More than 50% of coding sequence deleted
    // ---

    // Find coding part of the transcript (i.e. no UTRs)
    Variant seqChange = changeEffect.getSeqChange();
    int cdsStart = tr.isStrandPlus() ? tr.getCdsStart() : tr.getCdsEnd();
    int cdsEnd = tr.isStrandPlus() ? tr.getCdsEnd() : tr.getCdsStart();
    Marker coding = new Marker(seqChange.getChromosome(), cdsStart, cdsEnd, 1, "");

    // Create an interval intersecting the CDS and the deletion
    int start = Math.max(cdsStart, seqChange.getStart());
    int end = Math.min(cdsEnd, seqChange.getEnd());
    if (start >= end) return false; // No intersections with coding part of the exon? => not LOF
    Marker codingDeleted = new Marker(seqChange.getChromosome(), start, end, 1, "");

    // Count:
    //   - number of coding bases deleted
    //   - number of coding bases
    int codingBasesDeleted = 0, codingBases = 0;
    for (Exon exon : tr) {
      codingBasesDeleted += codingDeleted.intersectSize(exon);
      codingBases += coding.intersectSize(exon);
    }

    // More than a threshold? => It is a LOF
    double percDeleted = codingBasesDeleted / ((double) codingBases);
    return (percDeleted > deleteProteinCodingBases);
  }