/// <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>
/// Did we gain a start codon in this 5'UTR interval?
/// </summary>
/// <param name="seqChange"></param>
/// <returns>A new start codon (if gained)</returns>
private string startGained(Variant seqChange)
{
if (!seqChange.isSnv())
{
return("");
} // Only SNPs supported.
// Calculate SNP position relative to UTRs
long pos = seqChange.DistanceBases(get5primeUtrs().OfType <Interval>().ToList(), IsStrandMinus());
// Change base at SNP position
string sequence = getSequence();
char[] chars = sequence.ToCharArray();
char snpBase = seqChange.NetChange(this)[0];
if (IsStrandMinus() && Alphabets.DNA.TryGetComplementSymbol((byte)snpBase, out byte complement))
{
snpBase = (char)complement;
}
chars[pos] = snpBase;
// Do we gain a new start codon?
return(startGained(chars, pos));
}
/// <summary>
/// We may have to calculate 'netCdsChange', which is the effect on the CDS.
/// Note: A deletion or a MNP might affect several exons
/// </summary>
/// <returns></returns>
protected override string NetCdsChange()
{
if (Variant.Length() > 1)
{
StringBuilder sb = new StringBuilder();
foreach (Exon exon in Transcript.ExonsSortedStrand)
{
string seq = Variant.NetChange(exon);
sb.Append(exon.IsStrandPlus() ? seq : SequenceExtensions.ConvertToString(new Sequence(Alphabets.AmbiguousDNA, seq).GetReverseComplementedSequence()));
}
return(sb.ToString());
}
return(Variant.NetChange(Transcript.IsStrandPlus()));
}
/// <summary>
/// Get new (modified) codons
/// </summary>
/// <returns></returns>
protected override string CodonsAlt()
{
// Inserts BEFORE base:
// - In positive strand that is BEFORE pos
// - In negative strand, that is AFTER pos
int idx = CodonStartIndex + (Transcript.IsStrandMinus() ? 1 : 0);
// Insertion: Concatenate...
string prefix = CodonsReference.Length >= idx?CodonsReference.Substring(0, idx) : CodonsReference; // First part of the codon
string netChange = Variant.NetChange(Transcript.IsStrandMinus()); // Insertion
string suffix = CodonsReference.Length >= idx?CodonsReference.Substring(idx) : ""; // last part of the codon
// New codon
string codonsNew = prefix + netChange + suffix;
return(codonsNew);
}
/// <summary>
/// We may have to calculate 'netCdsChange', which is the effect on the CDS.
/// Note: A deletion or a MNP might affect several exons
/// </summary>
/// <returns></returns>
protected virtual string NetCdsChange()
{
if (!RequireNetCdsChange)
{
return("");
}
if (Variant.Length() > 1)
{
StringBuilder sb = new StringBuilder();
foreach (Exon exon in Transcript.ExonsSortedStrand)
{
sb.Append(Variant.NetChange(exon));
}
return(sb.ToString());
}
return(Variant.NetChange(Transcript.IsStrandMinus()));
}
/// <summary>
/// Get new (modified) codons
/// </summary>
/// <returns></returns>
protected override string CodonsAlt()
{
// Was there a problem getting 'codonsOld'? => We cannot do anything
if (CodonsReference == "")
{
return("");
}
char[] codonChars = CodonsReference.ToLower(CultureInfo.InvariantCulture).ToCharArray();
char snpBase = Variant.NetChange(Transcript.IsStrandMinus())[0];
if (CodonStartIndex < codonChars.Length)
{
codonChars[CodonStartIndex] = char.ToUpper(snpBase);
}
string codonsNew = new string(codonChars);
return(codonsNew);
}
protected void ApplyIns(Variant variant, IntervalSequence markerSeq)
{
// Get sequence in positive strand direction
ISequence seq = IsStrandPlus() ? Sequence : Sequence.GetReverseComplementedSequence();
// Apply change to sequence
String netChange = variant.NetChange(this);
long idx = variant.OneBasedStart - OneBasedStart - 1;
if (idx >= 0)
{
seq = new Sequence(seq.Alphabet, SequenceExtensions.ConvertToString(seq, 0, idx + 1) + netChange + SequenceExtensions.ConvertToString(seq, idx + 1));
}
else
{
seq = new Sequence(seq.Alphabet, netChange + SequenceExtensions.ConvertToString(seq));
}
// Update sequence
markerSeq.Sequence = IsStrandPlus() ? seq : seq.GetReverseComplementedSequence();
}