public void DetermineIntronicEffect_IsStartSpliceSite()
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, new Interval(300, 303), VariantType.deletion);
Assert.True(positionalEffect.IsStartSpliceSite);
}
public void IsFivePrimeUtrVariant(bool onReverseStrand, bool withinCdna, bool beforeCoding, bool afterCoding,
bool expectedResult)
{
var positionalEffect = new TranscriptPositionalEffect
{
BeforeCoding = beforeCoding,
AfterCoding = afterCoding,
WithinCdna = withinCdna
};
var variant = new Mock <ISimpleVariant>();
var transcript = new Mock <ITranscript>();
variant.SetupGet(x => x.AltAllele).Returns("G");
variant.SetupGet(x => x.RefAllele).Returns("C");
var variantEffect = new VariantEffect(positionalEffect, variant.Object, transcript.Object, "", "", "", "",
null, "", "");
var gene = new Mock <IGene>();
transcript.SetupGet(x => x.Gene).Returns(gene.Object);
gene.SetupGet(x => x.OnReverseStrand).Returns(onReverseStrand);
var translation = new Mock <ITranslation>();
transcript.SetupGet(x => x.Translation).Returns(translation.Object);
Assert.Equal(expectedResult, variantEffect.IsFivePrimeUtrVariant());
}
public void IsWithinCds_ReturnFalse()
{
var positionalEffect = new TranscriptPositionalEffect();
var observedResult = positionalEffect.IsWithinCds(-1, -1, null, null);
Assert.False(observedResult);
}
public void IsWithinCds_ReturnTrue()
{
var positionalEffect = new TranscriptPositionalEffect();
var observedResult = positionalEffect.IsWithinCds(180, 180, null, null);
Assert.True(observedResult);
}
public void DetermineIntronicEffect_IsEndSpliceSite()
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, new Interval(400, 400), VariantType.SNV);
Assert.True(positionalEffect.IsEndSpliceSite);
}
public void DetermineIntronicEffect_IsWithinFrameshiftIntron()
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, new Interval(702, 705), VariantType.deletion);
Assert.True(positionalEffect.IsWithinFrameshiftIntron);
}
public void DetermineIntronicEffect_IsWithinSpliceSiteRegion()
{
var positionalEffect = new TranscriptPositionalEffect();
IInterval variant = new Interval(298, 302);
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, variant, VariantType.deletion);
Assert.True(positionalEffect.IsWithinSpliceSiteRegion);
}
public void DetermineIntronicEffect_IsWithinFrameshiftIntron_NotInSpliceSite()
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, new Interval(701, 709), VariantType.deletion);
Assert.True(positionalEffect.IsWithinFrameshiftIntron);
Assert.False(positionalEffect.IsStartSpliceSite);
Assert.False(positionalEffect.IsEndSpliceSite);
}
public void DetermineExonicEffect_WithinCdna()
{
IInterval variant = new Interval(879600, 879600);
var position = new MappedPosition(1692, 1692, -1, -1, -1, -1, 7, 7, -1, -1, 12, 12);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineExonicEffect(_forwardTranscript.Object, variant, position, 1692, 1692, -1, -1, "G", false);
Assert.True(positionalEffect.WithinCdna);
}
public void DetermineExonicEffect_WithinCds()
{
IInterval variant = new Interval(876543, 876543);
var position = new MappedPosition(206, 206, 206, 206, 69, 69, 2, 2, -1, -1, 2, 2);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineExonicEffect(_forwardTranscript.Object, variant, position, 206, 206, 206, 206, "G", false);
Assert.True(positionalEffect.WithinCdna);
}
public void DetermineExonicEffect_OverlapWithMicroRna()
{
IInterval variant = new Interval(3477284, 3477284);
var position = new MappedPosition(71, 71, -1, -1, -1, -1, 1, 1, -1, -1, 0, 0);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineExonicEffect(_reverseTranscript.Object, variant, position, 71, 71, -1, -1, "G", false);
Assert.True(positionalEffect.OverlapWithMicroRna);
}
public void DetermineExonicEffect_HasExonOverlap()
{
IInterval variant = new Interval(876686, 876686);
var position = new MappedPosition(349, 349, 349, 349, 117, 117, 2, 2, -1, -1, 2, 2);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineExonicEffect(_forwardTranscript.Object, variant, position, 349, 349, 349, 349, "G", false);
Assert.True(positionalEffect.HasExonOverlap);
}
public void IsWithinCds_IsWithinFrameshiftIntron_ReturnFalse()
{
var variant = new Interval(100, 101);
var codingRegion = new Interval(102, 120);
var positionalEffect = new TranscriptPositionalEffect {
IsWithinFrameshiftIntron = true
};
var observedResult = positionalEffect.IsWithinCds(-1, -1, codingRegion, variant);
Assert.False(observedResult);
}
private static VariantEffect GetVariantEffect(ITranscript transcript, ISimpleVariant variant, IMappedPositions mappedPositions, string refAminoAcids, string altAminoAcids, string refCodons, string altCodons, bool insertionInStartAndNoImpact)
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(transcript.Introns, variant, variant.Type);
positionalEffect.DetermineExonicEffect(transcript, variant, mappedPositions, variant.AltAllele, insertionInStartAndNoImpact);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, refAminoAcids,
altAminoAcids,
refCodons, altCodons, mappedPositions.ProteinInterval.Start);
return(variantEffect);
}
public void DetermineIntronicEffect_IsWithinIntron()
{
IInterval variant = new Interval(300, 302);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(_otherTranscriptRegions, variant, VariantType.deletion);
Assert.False(positionalEffect.IsWithinIntron);
IInterval variant2 = new Interval(303, 303);
var positionalEffect2 = new TranscriptPositionalEffect();
positionalEffect2.DetermineIntronicEffect(_otherTranscriptRegions, variant2, VariantType.deletion);
Assert.True(positionalEffect2.IsWithinIntron);
}
private static TranscriptPositionalEffect GetPositionalEffect(ITranscript transcript, ISimpleVariant variant,
IMappedPosition position, string refAminoAcid, string altAminoAcid, int coveredCdnaStart,
int coveredCdnaEnd, int coveredCdsStart, int coveredCdsEnd)
{
bool startCodonInsertionWithNoImpact = variant.Type == VariantType.insertion &&
position.ProteinStart <= 1 &&
altAminoAcid.EndsWith(refAminoAcid);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(transcript.TranscriptRegions, variant, variant.Type);
positionalEffect.DetermineExonicEffect(transcript, variant, position, coveredCdnaStart, coveredCdnaEnd,
coveredCdsStart, coveredCdsEnd, variant.AltAllele, startCodonInsertionWithNoImpact);
return(positionalEffect);
}
public void DetermineIntronicEffect_NotWithinFrameshiftIntron()
{
var transcriptRegions = new ITranscriptRegion[]
{
new TranscriptRegion(TranscriptRegionType.Exon, 1, 201342300, 201342340, 1, 186),
new TranscriptRegion(TranscriptRegionType.Intron, 1, 201342340, 201342343, 186, 187),
new TranscriptRegion(TranscriptRegionType.Exon, 2, 201342344, 201342400, 187, 349)
};
IInterval variant = new Interval(201342344, 201342344);
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(transcriptRegions, variant, VariantType.SNV);
Assert.True(positionalEffect.IsWithinSpliceSiteRegion);
}
public void DetermineIntronicEffect_NullIntrons()
{
var positionalEffect = new TranscriptPositionalEffect();
positionalEffect.DetermineIntronicEffect(null, new Interval(400, 400), VariantType.SNV);
Assert.False(positionalEffect.IsEndSpliceSite);
Assert.False(positionalEffect.IsStartSpliceSite);
Assert.False(positionalEffect.IsWithinFrameshiftIntron);
Assert.False(positionalEffect.IsWithinIntron);
Assert.False(positionalEffect.IsWithinSpliceSiteRegion);
Assert.False(positionalEffect.HasExonOverlap);
Assert.False(positionalEffect.AfterCoding);
Assert.False(positionalEffect.BeforeCoding);
Assert.False(positionalEffect.WithinCdna);
Assert.False(positionalEffect.WithinCds);
Assert.False(positionalEffect.HasFrameShift);
Assert.False(positionalEffect.IsCoding);
}
public void IsStopLost_DeletionOverStopCodon_ReturnTrue()
{
var positionalEffect = new TranscriptPositionalEffect
{
BeforeCoding = false,
AfterCoding = true,
WithinCdna = true
};
var variant = new Mock <ISimpleVariant>();
variant.SetupGet(x => x.AltAllele).Returns("ATAGCCC");
variant.SetupGet(x => x.RefAllele).Returns("A");
var variantEffect = new VariantEffect(positionalEffect, variant.Object, null, "", "", "", "",
null, "*", "X");
Assert.True(variantEffect.IsStopLost());
}
public void IsCodingSequenceVariant_WithMoreSpecificConsequence_ReturnFalse(ConsequenceTag ct)
{
var positionalEffect = new TranscriptPositionalEffect
{
BeforeCoding = false,
AfterCoding = true,
WithinCdna = true
};
var cache = new VariantEffectCache();
cache.Add(ct, true);
var variant = new Mock <ISimpleVariant>();
variant.SetupGet(x => x.AltAllele).Returns("ATAGCCC");
variant.SetupGet(x => x.RefAllele).Returns("A");
var variantEffect = new VariantEffect(positionalEffect, variant.Object, null, "", "", "", "",
null, null, null, cache);
Assert.False(variantEffect.IsCodingSequenceVariant());
}
public void IsSpliceDonorVariant(bool onReverseStrand, bool isStartSpliceSite, bool isEndSpliceSite, bool expectedResult)
{
var positionalEffect = new TranscriptPositionalEffect
{
IsStartSpliceSite = isStartSpliceSite,
IsEndSpliceSite = isEndSpliceSite
};
var variant = new Mock <ISimpleVariant>();
var transcript = new Mock <ITranscript>();
variant.SetupGet(x => x.AltAllele).Returns("G");
variant.SetupGet(x => x.RefAllele).Returns("C");
var variantEffect = new VariantEffect(positionalEffect, variant.Object, transcript.Object, "", "", "", "",
null, "", "");
var gene = new Mock <IGene>();
transcript.SetupGet(x => x.Gene).Returns(gene.Object);
gene.SetupGet(x => x.OnReverseStrand).Returns(onReverseStrand);
Assert.Equal(expectedResult, variantEffect.IsSpliceDonorVariant());
}
public void IsWithinCdna(int cdnaStart, int cdnaEnd, int totalExonLen, bool expectedResult)
{
var observedResult = TranscriptPositionalEffect.IsWithinCdna(cdnaStart, cdnaEnd, totalExonLen);
Assert.Equal(expectedResult, observedResult);
}
public void IsBeforeCoding_True_WhenInsertion()
{
var observedResult = TranscriptPositionalEffect.IsBeforeCoding(101, 100, 100, 101);
Assert.True(observedResult);
}
public void DetermineSmallVariantEffects_tier3()
{
var cache = new VariantEffectCache();
cache.Add(ConsequenceTag.mature_miRNA_variant, false);
cache.Add(ConsequenceTag.splice_donor_variant, true);
cache.Add(ConsequenceTag.splice_acceptor_variant, true);
cache.Add(ConsequenceTag.stop_gained, true);
cache.Add(ConsequenceTag.frameshift_variant, true);
cache.Add(ConsequenceTag.stop_lost, true);
cache.Add(ConsequenceTag.start_lost, true);
cache.Add(ConsequenceTag.inframe_insertion, true);
cache.Add(ConsequenceTag.inframe_deletion, true);
cache.Add(ConsequenceTag.missense_variant, true);
cache.Add(ConsequenceTag.protein_altering_variant, true);
cache.Add(ConsequenceTag.splice_region_variant, true);
cache.Add(ConsequenceTag.incomplete_terminal_codon_variant, true);
cache.Add(ConsequenceTag.stop_retained_variant, true);
cache.Add(ConsequenceTag.synonymous_variant, true);
cache.Add(ConsequenceTag.coding_sequence_variant, true);
cache.Add(ConsequenceTag.five_prime_UTR_variant, true);
cache.Add(ConsequenceTag.three_prime_UTR_variant, true);
cache.Add(ConsequenceTag.non_coding_transcript_exon_variant, true);
cache.Add(ConsequenceTag.intron_variant, true);
cache.Add(ConsequenceTag.NMD_transcript_variant, true);
cache.Add(ConsequenceTag.non_coding_transcript_variant, true);
var simpleVariant = new Mock <ISimpleVariant>();
simpleVariant.SetupGet(x => x.RefAllele).Returns("G");
simpleVariant.SetupGet(x => x.AltAllele).Returns("C");
var positionalEffect = new TranscriptPositionalEffect
{
IsWithinIntron = true
};
var variantEffect = new VariantEffect(positionalEffect, simpleVariant.Object, null, null, null, null, null, null, cache);
var featureEffect = new Mock <IFeatureVariantEffects>();
featureEffect.Setup(x => x.Ablation()).Returns(false);
featureEffect.Setup(x => x.Amplification()).Returns(false);
featureEffect.Setup(x => x.Truncation()).Returns(true);
featureEffect.Setup(x => x.Elongation()).Returns(true);
var consequence = new Consequences(variantEffect, featureEffect.Object);
consequence.DetermineSmallVariantEffects();
var observedConsequence = consequence.GetConsequences();
Assert.Equal(ConsequenceTag.splice_donor_variant, observedConsequence[0]);
Assert.Equal(ConsequenceTag.splice_acceptor_variant, observedConsequence[1]);
Assert.Equal(ConsequenceTag.stop_gained, observedConsequence[2]);
Assert.Equal(ConsequenceTag.frameshift_variant, observedConsequence[3]);
Assert.Equal(ConsequenceTag.stop_lost, observedConsequence[4]);
Assert.Equal(ConsequenceTag.start_lost, observedConsequence[5]);
Assert.Equal(ConsequenceTag.inframe_insertion, observedConsequence[6]);
Assert.Equal(ConsequenceTag.inframe_deletion, observedConsequence[7]);
Assert.Equal(ConsequenceTag.missense_variant, observedConsequence[8]);
Assert.Equal(ConsequenceTag.protein_altering_variant, observedConsequence[9]);
Assert.Equal(ConsequenceTag.splice_region_variant, observedConsequence[10]);
Assert.Equal(ConsequenceTag.incomplete_terminal_codon_variant, observedConsequence[11]);
Assert.Equal(ConsequenceTag.stop_retained_variant, observedConsequence[12]);
Assert.Equal(ConsequenceTag.synonymous_variant, observedConsequence[13]);
Assert.Equal(ConsequenceTag.coding_sequence_variant, observedConsequence[14]);
Assert.Equal(ConsequenceTag.five_prime_UTR_variant, observedConsequence[15]);
Assert.Equal(ConsequenceTag.three_prime_UTR_variant, observedConsequence[16]);
Assert.Equal(ConsequenceTag.non_coding_transcript_exon_variant, observedConsequence[17]);
Assert.Equal(ConsequenceTag.intron_variant, observedConsequence[18]);
Assert.Equal(ConsequenceTag.NMD_transcript_variant, observedConsequence[19]);
Assert.Equal(ConsequenceTag.non_coding_transcript_variant, observedConsequence[20]);
}
public void IsMatureMirnaVariant_NullMirnas()
{
var observedResult = TranscriptPositionalEffect.IsMatureMirnaVariant(-1, -1, null, true);
Assert.False(observedResult);
}
