public void ValidateLookupWithOffsetValueSix()
{
string alphabetName = utilityObj.xmlUtil.GetTextValue(
Constants.SimpleRnaAlphabetNode, Constants.AlphabetNameNode);
string expectedSeq = utilityObj.xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.ExpectedNormalString);
string expectedAminoAcid = utilityObj.xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.OffsetZeroSixCharsAminoAcidV2);
string expectedOffset = utilityObj.xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.OffsetVaule2);
Sequence seq = new Sequence(Utility.GetAlphabet(alphabetName), expectedSeq);
// Validate Codons lookup method.
string aminoAcid = Codons.Lookup(seq, Convert.ToInt32(expectedOffset, null)).ToString();
// Validate amino acids for a given sequence.
Assert.AreEqual(expectedAminoAcid, aminoAcid);
ApplicationLog.WriteLine(string.Format((IFormatProvider)null,
"Translation P1: Amino Acid {0} is expected.", aminoAcid));
ApplicationLog.WriteLine(
"Translation P1: Amino Acid validation for a given sequence was completed successfully.");
}
AltAminoAcids, string RefCodons, string AltCodons, string TranscriptAltAllele) AnnotateTranscript(ITranscript transcript, ISimpleVariant variant, AminoAcids aminoAcids, ISequence refSequence)
{
var onReverseStrand = transcript.Gene.OnReverseStrand;
var start = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.Start);
var end = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.End);
var position = GetMappedPosition(transcript.TranscriptRegions, start.Region, start.Index, end.Region,
end.Index, variant, onReverseStrand, transcript.Translation?.CodingRegion, transcript.StartExonPhase,
variant.Type == VariantType.insertion);
var transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, onReverseStrand);
var codingSequence = GetCodingSequence(transcript, refSequence);
var codons = Codons.GetCodons(transcriptAltAllele, position.CdsStart, position.CdsEnd,
position.ProteinStart, position.ProteinEnd, codingSequence);
var coveredCdna = transcript.TranscriptRegions.GetCoveredCdnaPositions(position.CdnaStart, start.Index,
position.CdnaEnd, end.Index, onReverseStrand);
var aa = aminoAcids.Translate(codons.Reference, codons.Alternate);
var coveredPositions = MappedPositionUtilities.GetCoveredCdsAndProteinPositions(coveredCdna.Start, coveredCdna.End,
transcript.StartExonPhase, transcript.Translation?.CodingRegion);
// only generate the covered version of ref & alt alleles when CDS start/end is -1
var coveredAa = position.CdsStart == -1 || position.CdsEnd == -1
? GetCoveredAa(aminoAcids, transcriptAltAllele, coveredPositions, codingSequence)
: aa;
var positionalEffect = GetPositionalEffect(transcript, variant, position, aa.Reference, aa.Alternate,
coveredCdna.Start, coveredCdna.End, coveredPositions.CdsStart, coveredPositions.CdsEnd);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, aa.Reference, aa.Alternate,
codons.Reference, codons.Alternate, position.ProteinStart, coveredAa.Reference, coveredAa.Alternate);
return(variantEffect, position, aa.Reference, aa.Alternate, codons.Reference, codons.Alternate,
transcriptAltAllele);
}
public void ValidateAminoAcid()
{
// Get Node values from XML.
string expectedNucleo = Utility._xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.Nucleotide);
string expectedAminoAcid = Utility._xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.AminoAcid);
// Create Nucleotide objects.
Nucleotide firstNucleo1 = new Nucleotide(expectedNucleo[0], "Uracil");
Nucleotide firstNucleo2 = new Nucleotide(expectedNucleo[1], "Uracil");
Nucleotide firstNucleo3 = new Nucleotide(expectedNucleo[2], "Uracil");
// Validate Codons lookup method.
AminoAcid aminoAcid = Codons.Lookup(firstNucleo1, firstNucleo2, firstNucleo3);
// Validate amino acids for each triplet.
Assert.AreEqual(aminoAcid.Name.ToString(), expectedAminoAcid);
ApplicationLog.WriteLine(string.Format(null,
"Translation BVT: Amino Acid {0} is expected.", aminoAcid));
ApplicationLog.WriteLine(
"Translation BVT: Amino Acid validation for a given triplets of nucleotide was completed successfully.");
}
public void ValidateLookupWithZeroOffset()
{
string alphabetName = _utilityObj._xmlUtil.GetTextValue(Constants.SimpleRnaAlphabetNode,
Constants.AlphabetNameNode);
string expectedSeq = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.SequenceWithmoreThanTweleveChars);
string expectedAminoAcid = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.OffsetOneMoreThanTwelveCharsAminoAcid);
string expectedOffset = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.OffsetVaule4);
ISequence seq = new Sequence(Utility.GetAlphabet(alphabetName), expectedSeq);
// Validate Codons lookup method.
AminoAcid aminoAcid = Codons.Lookup(seq, Convert.ToInt32(expectedOffset, null));
// Validate amino acids for a given sequence.
Assert.AreEqual(aminoAcid.Name.ToString((IFormatProvider)null), expectedAminoAcid);
ApplicationLog.WriteLine(string.Format((IFormatProvider)null,
"Translation P2: Amino Acid {0} is expected.", aminoAcid));
ApplicationLog.WriteLine(
"Translation P2: Amino Acid validation for a given sequence was completed successfully.");
}
public void ValidateLookupWithSixChars()
{
string alphabetName = Utility._xmlUtil.GetTextValue(
Constants.SimpleRnaAlphabetNode, Constants.AlphabetNameNode);
string expectedSeq = Utility._xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.SequenceWithSixChars);
string expectedAminoAcid = Utility._xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.OffsetZeroSixCharsAminoAcid);
string expectedOffset = Utility._xmlUtil.GetTextValue(
Constants.CodonsNode, Constants.OffsetVaule2);
ISequence seq = new Sequence(Utility.GetAlphabet(alphabetName), expectedSeq);
// Validate Codons lookup method.
AminoAcid aminoAcid = Codons.Lookup(seq, Convert.ToInt32(expectedOffset, null));
// Validate amino acids for a given sequencet.
Assert.AreEqual(aminoAcid.Name.ToString(), expectedAminoAcid);
ApplicationLog.WriteLine(string.Format(null,
"Translation P1: Amino Acid {0} is expected.", aminoAcid));
ApplicationLog.WriteLine(
"Translation P1: Amino Acid validation for a given sequence was completed successfully.");
}
public void ValidateAminoAcidForSequence()
{
// Get Node values from XML.
string alphabetName = _utilityObj._xmlUtil.GetTextValue(Constants.SimpleRnaAlphabetNode,
Constants.AlphabetNameNode);
string expectedSeq = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.ExpectedNormalString);
string expectedAminoAcid = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.SeqAminoAcid);
string expectedOffset = _utilityObj._xmlUtil.GetTextValue(Constants.CodonsNode,
Constants.OffsetVaule1);
ISequence seq = new Sequence(Utility.GetAlphabet(alphabetName), expectedSeq);
// Validate Codons lookup method.
AminoAcid aminoAcid = Codons.Lookup(seq, Convert.ToInt32(expectedOffset, null));
// Validate amino acids for each triplet.
Assert.AreEqual(aminoAcid.Name.ToString((IFormatProvider)null), expectedAminoAcid);
ApplicationLog.WriteLine(string.Format((IFormatProvider)null,
"Translation BVT: Amino Acid {0} is expected.", aminoAcid));
ApplicationLog.WriteLine(
"Translation BVT: Amino Acid validation for a given sequence was completed successfully.");
}
/// <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>
/// Get AA for a single DNA codon
/// </summary>
/// <param name="codon"></param>
/// <param name="aa"></param>
/// <returns></returns>
public static bool TranslateDnaCodon(string codon, out byte aa)
{
ISequence rnaCodon = Transcription.Transcribe(new Sequence(Alphabets.DNA, codon.Select(c => (byte)c).ToArray()));
return(Codons.TryLookup(rnaCodon, 0, out aa));
}
private static SequenceChange GetCoveredAa(AminoAcids aminoAcids, string transcriptAltAllele, int coveredCdsStart, int coveredCdsEnd, int coveredProteinStart, int coveredProteinEnd, ISequence codingSequence)
{
var codonsChange = Codons.GetCodons(transcriptAltAllele, coveredCdsStart, coveredCdsEnd, coveredProteinStart, coveredProteinEnd, codingSequence);
return(aminoAcids.Translate(codonsChange.Reference, codonsChange.Alternate));
}
public void IsTriplet(int len, bool expectedResult)
{
var observedResult = Codons.IsTriplet(len);
Assert.Equal(expectedResult, observedResult);
}
