/// <summary>
/// returns true if the variant is a protein altering variant [VariationEffect.pm:300 protein_altering_variant]
/// </summary>
public bool IsProteinAlteringVariant()
{
const ConsequenceType ct = ConsequenceType.ProteinAlteringVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
if (_altAllele.IsStructuralVariant)
{
_cache.Add(ct, false);
return(false);
}
var result = true;
var sameLen = _preCache.ReferenceAminoAcidsLen == _preCache.AlternateAminoAcidsLen;
var startsWithTer = _preCache.ReferenceAminoAcids.StartsWith("X") || _preCache.AlternateAminoAcids.StartsWith("X");
var isInframeDeletion = IsInframeDeletion();
// Note: sequence ontology says that stop retained should not be here (http://www.sequenceontology.org/browser/current_svn/term/SO:0001567)
var isStopCodonVarinat = IsStopLost() || IsStopGained();//|| IsStopRetained()
if (sameLen || startsWithTer || isInframeDeletion || isStopCodonVarinat ||
IsStartLost() || IsFrameshiftVariant() || IsInframeInsertion() || IsStopRetained() || !_preCache.IsCoding)
{
result = false;
}
_cache.Add(ct, result);
return(result);
}
public bool IsGeneFusion()
{
const ConsequenceType ct = ConsequenceType.GeneFusion;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
if (_ta.BreakendTranscriptAnnotation == null || _ta.BreakendPos2Annotations == null ||
_ta.BreakendPos2Annotations.Count <= 0 || !_ta.BreakendTranscriptAnnotation.InCodingRegion)
{
_cache.Add(ConsequenceType.GeneFusion, false);
return(false);
}
var result = _ta.BreakendPos2Annotations.Any(
x =>
x.GeneName != _ta.BreakendTranscriptAnnotation.GeneName && x.InCodingRegion &&
!x.IsTranscriptCodingRegionOverlapped(_ta.BreakendTranscriptAnnotation) &&
x.TranscriptDataSource == _ta.BreakendTranscriptAnnotation.TranscriptDataSource);
_cache.Add(ConsequenceType.GeneFusion, result);
return(result);
}
/// <summary>
/// returns true if the variant is a splice region variant [VariationEffect.pm:483 splice_region]
/// </summary>
public bool IsSpliceRegionVariant()
{
const ConsequenceType ct = ConsequenceType.SpliceRegionVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
if (IsSpliceDonorVariant())
{
// false
}
else if (IsSpliceAcceptorVariant())
{
// false
}
else if (IsEssentialSpliceSite())
{
// false
}
else
{
result = _ta.IsWithinSpliceSiteRegion;
}
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the corresponding value has been cached
/// </summary>
public void Add(ConsequenceType consequence, bool result)
{
var index = (int)consequence;
_isCached[index] = true;
_cachedResults[index] = result;
}
/// <summary>
/// returns true if the variant is a 3' UTR variant [VariationEffect.pm:609 within_3_prime_utr]
/// </summary>
public bool IsThreePrimeUtrVariant()
{
const ConsequenceType ct = ConsequenceType.ThreePrimeUtrVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant && _transcript.Translation != null)
{
var hasTranslation = _transcript.Translation != null;
var isThreePrimeOfCoding = _transcript.Gene.OnReverseStrand
? IsBeforeCoding(_altAllele.Start, _altAllele.End, _transcript.Start, _transcript.Translation.CodingRegion.GenomicStart, hasTranslation)
: IsAfterCoding(_altAllele.Start, _altAllele.End, _transcript.End, _transcript.Translation.CodingRegion.GenomicEnd, hasTranslation);
result = isThreePrimeOfCoding && IsWithinCdna();
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a stop retained variant [VariationEffect.pm:701 stop_lost]
/// </summary>
public bool IsStopRetained()
{
const ConsequenceType ct = ConsequenceType.StopRetainedVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
var alternateAminoAcids = TrimPeptides(_ta.AlternateAminoAcids);
if (!_altAllele.IsStructuralVariant)
{
result = _ta.ReferenceAminoAcids != null && alternateAminoAcids != null &&
_ta.ReferenceAminoAcids == alternateAminoAcids &&
_ta.ReferenceAminoAcids.Contains(AminoAcids.StopCodon) ||
string.IsNullOrEmpty(_ta.ReferenceAminoAcids) && alternateAminoAcids != null &&
_ta.ProteinBegin == _transcript.Translation.PeptideSeq.Length + 1 &&
alternateAminoAcids == AminoAcids.StopCodon;
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if we have an incomplete terminal codon variant. [VariantEffect.pm:983 partial_codon]
/// </summary>
public bool IsIncompleteTerminalCodonVariant()
{
const ConsequenceType ct = ConsequenceType.IncompleteTerminalCodonVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
if (_transcript.Translation == null || _altAllele.IsStructuralVariant)
{
_cache.Add(ct, false);
return(false);
}
int cdsLength = CodingSequence.GetCodingSequenceLength(_transcript.CdnaMaps,
_transcript.Translation.CodingRegion.GenomicStart, _transcript.Translation.CodingRegion.GenomicEnd,
_transcript.StartExonPhase);
int codonCdsStart = _ta.ProteinBegin * 3 - 2;
int lastCodonLength = cdsLength - (codonCdsStart - 1);
bool result = lastCodonLength < 3 && lastCodonLength > 0;
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if at least one base of the first codon was changed in the transcript [VariantEffect.pm:722 affects_start_codon]
/// </summary>
public bool IsStartLost()
{
const ConsequenceType ct = ConsequenceType.StartLost;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
// check the predicates
if (!_preCache.IsCoding)
{
_cache.Add(ct, false);
return(false);
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
if (_ta.ProteinBegin != 1 || _preCache.ReferenceAminoAcidsLen == 0)
{
_cache.Add(ct, false);
return(false);
}
result = _preCache.AlternateAminoAcidsLen == 0 || _preCache.AlternateAminoAcids[0] != _preCache.ReferenceAminoAcids[0];
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant overlaps a mature MiRNA. [VariationEffect.pm:432 within_mature_miRNA]
/// </summary>
public bool IsMatureMirnaVariant()
{
const ConsequenceType ct = ConsequenceType.MatureMirnaVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (_transcript.BioType == BioType.miRNA && !_altAllele.IsStructuralVariant)
{
if (_transcript.MicroRnas != null)
{
if (_transcript.MicroRnas.Any(microRna => microRna.Overlaps(_ta.ComplementaryDnaBegin, _ta.ComplementaryDnaEnd)))
{
result = true;
}
}
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a non-coding transcript exon variant [VariationEffect.pm:405 non_coding_exon_variant]
/// </summary>
public bool IsNonCodingTranscriptExonVariant()
{
const ConsequenceType ct = ConsequenceType.NonCodingTranscriptExonVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = !_altAllele.IsStructuralVariant && _ta.HasExonOverlap && IsNonCodingTranscriptVariant();
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is an inframe deletion [VariantEffect.pm:825 inframe_deletion]
/// </summary>
public bool IsInframeDeletion()
{
const ConsequenceType ct = ConsequenceType.InframeDeletion;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
// check the predicates
if (!_preCache.IsCoding || !_preCache.IsDeletion)
{
_cache.Add(ct, false);
return(false);
}
if (!_altAllele.IsStructuralVariant)
{
if (_preCache.ReferenceCodonLen == 0 || //|| (PreCache.ReferenceCodonLen < PreCache.AlternateCodonLen)
IsFrameshiftVariant() ||
IsIncompleteTerminalCodonVariant() ||
IsStopGained())
{
_cache.Add(ct, false);
return(false);
}
// simple string match
var referenceCodon = _preCache.ReferenceCodon.ToLower();
var alternateCodon = _preCache.AlternateCodon.ToLower();
if (referenceCodon.StartsWith(alternateCodon) || referenceCodon.EndsWith(alternateCodon))
{
_cache.Add(ct, true);
return(true);
}
// try a more complex string match
var commonPrefixLength = _preCache.ReferenceCodon.CommonPrefixLength(_preCache.AlternateCodon);
var commonSuffixLength = _preCache.ReferenceCodon.CommonSuffixLength(_preCache.AlternateCodon);
_preCache.AlternateCodonLen = _preCache.AlternateCodonLen - commonPrefixLength - commonSuffixLength;
result = _preCache.AlternateCodonLen == 0;
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is within a non-coding gene [VariationEffect.pm:398 within_non_coding_gene]
/// </summary>
public bool IsNonCodingTranscriptVariant()
{
const ConsequenceType ct = ConsequenceType.NonCodingTranscriptVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
// TODO: Isn't IsWithinTranscript always true? and not within mature miRNA is always true
// For Ensembl transcript, miRNA may be a valid attribute. We have their location and we would like to check if the variant overlaps with the miRNA
var result = !_altAllele.IsStructuralVariant && _transcript.Translation == null && !IsMatureMirnaVariant();
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a splice acceptor variant [VariationEffect.pm:404 acceptor_splice_site]
/// </summary>
public bool IsSpliceAcceptorVariant()
{
const ConsequenceType ct = ConsequenceType.SpliceAcceptorVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
result = _transcript.Gene.OnReverseStrand ? _ta.IsStartSpliceSite : _ta.IsEndSpliceSite;
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant's amino acid changes to a stop codon [VariationEffect.pm:884 stop_gained]
/// </summary>
public bool IsStopGained()
{
const ConsequenceType ct = ConsequenceType.StopGained;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
result = !IsStopRetained() && (_ta.ReferenceAminoAcids == null || !_ta.ReferenceAminoAcids.Contains(AminoAcids.StopCodon)) && _ta.AlternateAminoAcids != null && _ta.AlternateAminoAcids.Contains(AminoAcids.StopCodon);
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a stop lost variant [VariationEffect.pm:898 stop_lost]
/// </summary>
public bool IsStopLost()
{
const ConsequenceType ct = ConsequenceType.StopLost;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant && !string.IsNullOrEmpty(_ta.ReferenceAminoAcids) && _ta.AlternateAminoAcids != null)
{
result = _ta.ReferenceAminoAcids.Contains(AminoAcids.StopCodon) &&
!_ta.AlternateAminoAcids.Contains(AminoAcids.StopCodon);
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is an inframe insertion [VariantEffect.pm:780 inframe_insertion]
/// </summary>
public bool IsInframeInsertion()
{
const ConsequenceType ct = ConsequenceType.InframeInsertion;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
// check the predicates
if (!_preCache.IsCoding || !_preCache.IsInsertion)
{
_cache.Add(ct, false);
return(false);
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
if (IsStopRetained() ||
IsFrameshiftVariant() ||
IsStartLost() ||
_preCache.AlternateCodonLen <= _preCache.ReferenceCodonLen ||
IsIncompleteTerminalCodonVariant())
{
_cache.Add(ct, false);
return(false);
}
if (!IsTruncatedByStop())
{
result = true;
}
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a synonymous variant [VariationEffect.pm:755 synonymous_variant]
/// </summary>
public bool IsSynonymousVariant()
{
const ConsequenceType ct = ConsequenceType.SynonymousVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
result = _ta.ReferenceAminoAcids != null &&
(_altAllele.VepVariantType == VariantType.SNV || _altAllele.VepVariantType == VariantType.MNV) &&
_ta.ReferenceAminoAcids == _ta.AlternateAminoAcids && !_ta.ReferenceAminoAcids.Contains("X") && !_ta.AlternateAminoAcids.Contains("X") && !IsStopRetained();
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a missense variant [VariantEffect.pm:682 missense_variant]
/// </summary>
public bool IsMissenseVariant()
{
const ConsequenceType ct = ConsequenceType.MissenseVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
// check the predicates
if (!_preCache.IsCoding)
{
_cache.Add(ct, false);
return(false);
}
if (_altAllele.IsStructuralVariant ||
IsStartLost() ||
IsStopLost() ||
IsStopGained() ||
IsIncompleteTerminalCodonVariant() ||
IsFrameshiftVariant() ||
IsInframeDeletion() ||
IsInframeInsertion())
{
_cache.Add(ct, false);
return(false);
}
if (_preCache.ReferenceAminoAcids != _preCache.AlternateAminoAcids &&
_preCache.ReferenceAminoAcidsLen == _preCache.AlternateAminoAcidsLen)
{
result = true;
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if it's a coding sequnce variant [VariationEffect.pm:998 coding_unknown]
/// </summary>
public bool IsCodingSequenceVariant()
{
const ConsequenceType ct = ConsequenceType.CodingSequenceVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
result = IsWithinCds() &&
(string.IsNullOrEmpty(_transcript.Translation.PeptideSeq) ||
string.IsNullOrEmpty(_ta.AlternateAminoAcids) || _ta.AlternateAminoAcids.Contains("X")) &&
!(IsFrameshiftVariant() || IsInframeDeletion() || IsIncompleteTerminalCodonVariant() || IsProteinAlteringVariant() || IsStopGained() || IsStopRetained());
}
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the variant is a frameshift variant [VariantEffect.pm:940 frameshift]
/// </summary>
public bool IsFrameshiftVariant()
{
const ConsequenceType ct = ConsequenceType.FrameshiftVariant;
if (_cache.Contains(ct))
{
return(_cache.Get(ct));
}
// check the predicates
if (!_preCache.IsCoding)
{
_cache.Add(ct, false);
return(false);
}
bool result = false;
if (!_altAllele.IsStructuralVariant)
{
if (IsIncompleteTerminalCodonVariant() || !_ta.HasValidCdsStart || !_ta.HasValidCdsEnd)
{
_cache.Add(ct, false);
return(false);
}
int varLen = _ta.CodingDnaSequenceEnd - _ta.CodingDnaSequenceBegin + 1;
int alleleLen = _altAllele.AlternateAllele?.Length ?? 0;
result = !Codons.IsTriplet(alleleLen - varLen) && !IsStopRetained();
}
result = result && !IsTruncatedByStop();
_cache.Add(ct, result);
return(result);
}
/// <summary>
/// returns true if the corresponding value has been cached
/// </summary>
public bool Contains(ConsequenceType consequence)
{
return(_isCached[(int)consequence]);
}
/// <summary>
/// returns the cached value for the corresponding result
/// </summary>
public bool Get(ConsequenceType consequence)
{
return(_cachedResults[(int)consequence]);
}