Package org.snpeff.snpEffect
Class LossOfFunction
java.lang.Object
org.snpeff.snpEffect.LossOfFunction
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
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Field Summary
FieldsModifier and TypeFieldDescriptionstatic final double
Larger deletions removing either the first exon or more than 50% of the protein-coding sequence of the affected transcriptstatic final double
It is assumed that even with a protein coding change at the last 5% of the protein, the protein could still be functional.static final double
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."double
double
double
static final int
Number of bases before last exon-exon junction that nonsense mediated decay is supposed to occurstatic final String
static final String
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Constructor Summary
Constructors -
Method Summary
Modifier and TypeMethodDescriptionboolean
isLof()
Can this collection of effects produce a "Loss of function"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 shiftsprotected boolean
isLofDeletion
(VariantEffect variantEffect) Is this deletion a LOF? Criteria: 1) First (coding) exon deleted 2) More than 50% of coding sequence deletedboolean
isNmd()
Can this collection of effects produce a "Nonsense mediated decay"?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 shiftsint
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()
Get LOF value for VCF info fieldGet NMD value for VCF info field
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Field Details
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VCF_INFO_NMD_NAME
- See Also:
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VCF_INFO_LOF_NAME
- See Also:
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MND_BASES_BEFORE_LAST_JUNCTION
public static final int MND_BASES_BEFORE_LAST_JUNCTIONNumber of bases before last exon-exon junction that nonsense mediated decay is supposed to occur- See Also:
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DEFAULT_IGNORE_PROTEIN_CODING_AFTER
public static final double DEFAULT_IGNORE_PROTEIN_CODING_AFTERIt is assumed that even with a protein coding change at the last 5% of the protein, the protein could still be functional.- See Also:
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DEFAULT_IGNORE_PROTEIN_CODING_BEFORE
public static final double DEFAULT_IGNORE_PROTEIN_CODING_BEFOREIt 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:
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DEFAULT_DELETE_PROTEIN_CODING_BASES
public static final double DEFAULT_DELETE_PROTEIN_CODING_BASESLarger deletions removing either the first exon or more than 50% of the protein-coding sequence of the affected transcript- See Also:
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ignoreProteinCodingAfter
public double ignoreProteinCodingAfter -
ignoreProteinCodingBefore
public double ignoreProteinCodingBefore -
deleteProteinCodingBases
public double deleteProteinCodingBases
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Constructor Details
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LossOfFunction
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Method Details
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isLof
public boolean isLof()Can this collection of effects produce a "Loss of function" -
isLof
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
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
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
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
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toStringVcfLof
Get LOF value for VCF info field -
toStringVcfNmd
Get NMD value for VCF info field
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