Class LossOfFunction

java.lang.Object
org.snpeff.snpEffect.LossOfFunction

public class LossOfFunction extends Object
Analyze if a set of effects are can create a "Loss Of Function" and "Nonsense mediated decays" effects. Of course, this is a prediction based on analysis of groups of "putative effects". Proper wet-lab validation is required to infer "real" LOF. References: I used the LOF definition used in the following paper "A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes", Science, 2012 From the paper: We adopted a definition for LoF variants expected to correlate with complete loss of function of the affected transcripts: stop codon-introducing (nonsense) or splice site-disrupting single-nucleotide variants (SNVs), insertion/deletion (indel) variants predicted to disrupt a transcript's reading frame, or larger deletions removing either the first exon or more than 50% of the protein-coding sequence of the affected transcript. Both nonsense SNVs and frameshift indels are enriched toward the 3' end of the affected gene, consistent with a greater tolerance to truncation close to the end of the coding sequence (Fig. 1C); putative LoF variants identified in the last 5% of the coding region were thus systematically removed from our high-confidence set.
Author:
pcingola
  • Field Details

    • VCF_INFO_NMD_NAME

      public static final String VCF_INFO_NMD_NAME
      See Also:
    • VCF_INFO_LOF_NAME

      public static final String VCF_INFO_LOF_NAME
      See Also:
    • MND_BASES_BEFORE_LAST_JUNCTION

      public static final int MND_BASES_BEFORE_LAST_JUNCTION
      Number of bases before last exon-exon junction that nonsense mediated decay is supposed to occur
      See Also:
    • DEFAULT_IGNORE_PROTEIN_CODING_AFTER

      public static final double DEFAULT_IGNORE_PROTEIN_CODING_AFTER
      It is assumed that even with a protein coding change at the last 5% of the protein, the protein could still be functional.
      See Also:
    • DEFAULT_IGNORE_PROTEIN_CODING_BEFORE

      public static final double DEFAULT_IGNORE_PROTEIN_CODING_BEFORE
      It is assumed that even with a protein coding change at the first 5% of the protein: "..suggesting some disrupted transcripts are rescued by transcriptional reinitiation at an alternative start codon."
      See Also:
    • DEFAULT_DELETE_PROTEIN_CODING_BASES

      public static final double DEFAULT_DELETE_PROTEIN_CODING_BASES
      Larger deletions removing either the first exon or more than 50% of the protein-coding sequence of the affected transcript
      See Also:
    • ignoreProteinCodingAfter

      public double ignoreProteinCodingAfter
    • ignoreProteinCodingBefore

      public double ignoreProteinCodingBefore
    • deleteProteinCodingBases

      public double deleteProteinCodingBases
  • Constructor Details

  • Method Details

    • isLof

      public boolean isLof()
      Can this collection of effects produce a "Loss of function"
    • isLof

      protected boolean isLof(VariantEffect variantEffect)
      Is this single change a LOF? 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
    • isLofDeletion

      protected boolean isLofDeletion(VariantEffect variantEffect)
      Is this deletion a LOF? Criteria: 1) First (coding) exon deleted 2) More than 50% of coding sequence deleted
    • isNmd

      public boolean isNmd()
      Can this collection of effects produce a "Nonsense mediated decay"?
    • isNmd

      protected boolean isNmd(VariantEffect variantEffect)
      Is this single change a LOF? 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
    • lastNmdPos

      public int lastNmdPos(Transcript tr)
      Find the last position where a nonsense mediated decay is supposed to occurr This is 50 bases (MND_BASES_BEFORE_LAST_JUNCTION bases) before the last exon-exon junction.
    • toString

      public String toString()
      Overrides:
      toString in class Object
    • toStringVcfLof

      public String toStringVcfLof()
      Get LOF value for VCF info field
    • toStringVcfNmd

      public String toStringVcfNmd()
      Get NMD value for VCF info field