/// <summary>
/// Analyze insertions in this transcript. Add changeEffect to 'changeEffect'
/// </summary>
/// <param name="exon"></param>
/// <returns></returns>
protected override bool ChangeCodon(Exon exon)
{
string netChange = Variant.NetChange(Transcript.IsStrandMinus());
CodonsReference = CodonsRef();
CodonsAlternate = CodonsAlt();
EffectType effType;
if (netChange.Length % CODON_SIZE != 0)
{
/**
* Length not multiple of CODON_SIZE => FRAME_SHIFT
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Insert 'TT' pos 0: TTA AAC CCG GGA AAC CCG GGA AAC CCG GG
* Insert 'TT' pos 1: ATT AAC CCG GGA AAC CCG GGA AAC CCG GG
* Insert 'TT' pos 2: AAT TAC CCG GGA AAC CCG GGA AAC CCG GG
*/
effType = EffectType.FRAME_SHIFT;
}
else if (CodonStartIndex == 0)
{
/**
* Length multiple of CODON_SIZE and insertion happens at codon boundary => CODON_INSERTION
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Insert 'TTT' pos 0: TTT AAA CCC GGG AAA CCC GGG AAA CCC GGG
*/
effType = EffectType.CODON_INSERTION;
}
else
{
/**
* Length multiple of CODON_SIZE and insertion does not happen at codon boundary => CODON_CHANGE_PLUS_CODON_INSERTION
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Insert 'TTT' pos 1: ATT TAA CCC GGG AAA CCC GGG AAA CCC GGG
* Insert 'TTT' pos 2: AAT TTA CCC GGG AAA CCC GGG AAA CCC GGG
*/
if (CodonsAlternate.ToUpper(CultureInfo.InvariantCulture).StartsWith(CodonsReference.ToUpper(CultureInfo.InvariantCulture)))
{
/**
* May be the inserted base are equal to the old ones.
* E.g.
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Insert 'AAA' pos 1: AAA AAA CCC GGG AAA CCC GGG AAA CCC GGG
*/
effType = EffectType.CODON_INSERTION;
}
else
{
effType = EffectType.CODON_CHANGE_PLUS_CODON_INSERTION;
}
}
Effect(exon, effType, false);
return(true);
}
/// <summary>
/// Calculate codons old / codons new
/// </summary>
protected void codonOldNew()
{
if (!Transcript.Intersects(Variant))
{
return;
}
// CDS coordinates
cdsStart = Transcript.IsStrandPlus() ? Transcript.CdsOneBasedStart : Transcript.CdsOneBasedEnd;
cdsEnd = Transcript.IsStrandPlus() ? Transcript.CdsOneBasedEnd : Transcript.CdsOneBasedStart;
// Does it intersect CDS?
if (cdsStart > Variant.OneBasedEnd)
{
return;
}
if (cdsEnd < Variant.OneBasedStart)
{
return;
}
// Base number relative to CDS start
long scStart, scEnd;
if (Transcript.IsStrandPlus())
{
scStart = cdsBaseNumber(Variant.OneBasedStart, false);
scEnd = cdsBaseNumber(Variant.OneBasedEnd, true);
}
else
{
scEnd = cdsBaseNumber(Variant.OneBasedStart, true);
scStart = cdsBaseNumber(Variant.OneBasedEnd, false);
}
// Update coordinates
CodonStartNumber = (int)(scStart / CODON_SIZE);
CodonStartIndex = (int)(scStart % CODON_SIZE);
// MNP overlap in coding part
long scLen = scEnd - scStart;
if (scLen < 0)
{
return;
}
// Round to codon position
long scStart3 = round3(scStart, false);
long scEnd3 = round3(scEnd, true);
long scLen3 = scEnd3 - scStart3;
if (scEnd3 == scStart3)
{
scEnd3 += 3;
} // At least one codon
// Append 'N'
string padN = "";
long diff = scEnd3 - (Transcript.RetrieveCodingSequence().Count - 1);
if (diff > 0)
{
scEnd3 = Transcript.RetrieveCodingSequence().Count - 1;
// Pad with 'N'
switch (diff)
{
case 1:
padN = "N";
break;
case 2:
padN = "NN";
break;
default:
throw new ArgumentOutOfRangeException("Sanity check failed. Number of 'N' pading is :" + diff + ". This should not happen!");
}
}
// Get old codon (reference)
CodonsReference = SequenceExtensions.ConvertToString(Transcript.RetrieveCodingSequence().GetSubSequence(scStart3, scLen3));
// Get new codon (change)
string prepend = CodonsReference.Substring(0, (int)(scStart - scStart3));
string append = scEnd3 > scEnd?CodonsReference.Substring(CodonsReference.Length - (int)(scEnd3 - scEnd)) : "";
CodonsAlternate = prepend + NetCdsChange() + append;
// Pad codons with 'N' if required
CodonsReference += padN;
CodonsAlternate += padN;
//---
// Can we simplify codons?
//---
if ((CodonsReference != null) && (CodonsAlternate != null))
{
while ((CodonsReference.Length >= 3) && (CodonsAlternate.Length >= 3))
{
// First codon
string cold = CodonsReference.Substring(0, 3);
string cnew = CodonsAlternate.Substring(0, 3);
// Are codons equal? => Simplify
if (cold.Equals(cnew, StringComparison.InvariantCultureIgnoreCase))
{
CodonsReference = CodonsReference.Substring(3);
CodonsAlternate = CodonsAlternate.Substring(3);
CodonStartNumber++;
}
else
{
break;
}
}
}
}
