public override bool CreateVariantEffect(Variant variant, VariantEffects variantEffects)
{
// Has the whole UTR been deleted?
if (variant.Includes(this) && variant.VarType == Variant.VariantType.DEL)
{
variantEffects.AddEffect(variant, this, EffectType.UTR_5_DELETED, ""); // A UTR was removed entirely
return(true);
}
// Add distance
Transcript tr = (Transcript)FindParent(typeof(Transcript));
long distance = utrDistance(variant, tr);
VariantEffect variantEffect = new VariantEffect(variant);
variantEffect.Set(this, IntervalType, EffectTypeMethods.EffectDictionary[IntervalType], distance >= 0 ? distance + " bases from TSS" : "");
variantEffect.Distance = distance;
variantEffects.AddEffect(variantEffect);
// Start gained?
string gained = startGained(variant);
if (gained != "")
{
variantEffects.AddEffect(variant, this, EffectType.START_GAINED, gained);
}
return(true);
}
/// <summary>
/// Apply a Variant to a marker. Variant is a duplication
/// </summary>
/// <param name="variant"></param>
/// <returns></returns>
protected Interval ApplyDup(Variant variant)
{
Interval m = new Interval(this);
if (variant.OneBasedEnd < m.OneBasedStart)
{
// Duplication before marker start? => Adjust both coordinates
long lenChange = variant.LengthChange();
m.OneBasedStart += lenChange;
m.OneBasedEnd += lenChange;
}
else if (variant.Includes(m))
{
// Duplication includes whole marker? => Adjust both coordinates
long lenChange = variant.LengthChange();
m.OneBasedStart += lenChange;
m.OneBasedEnd += lenChange;
}
else if (m.Includes(variant))
{
// Duplication included in marker? => Adjust end coordinate
m.OneBasedEnd += variant.LengthChange();
}
else if (variant.Intersects(m))
{
// Duplication includes part of marker? => Adjust end
m.OneBasedEnd += variant.IntersectSize(m);
}
else
{
// Duplication after end, no effect on marker coordinates
}
return(m);
}
/// <summary>
/// Apply a Variant to a marker. Variant is a deletion
/// </summary>
/// <param name="variant"></param>
/// <returns></returns>
protected Interval ApplyDel(Variant variant)
{
Interval m = new Interval(this);
if (variant.OneBasedEnd < m.OneBasedStart)
{
// Deletion before start: Adjust coordinates
long lenChange = variant.LengthChange();
m.OneBasedStart += lenChange;
m.OneBasedEnd += lenChange;
}
else if (variant.Includes(m))
{
// Deletion completely includes this marker => The whole marker deleted
return(null);
}
else if (m.Includes(variant))
{
// This marker completely includes the deletion, but deletion does not include
// marker. Marker is shortened (i.e. only 'end' coordinate needs to be updated)
m.OneBasedEnd += variant.LengthChange();
}
else
{
// Variant is partially included in this marker.
// This is treated as three different type of deletions:
// 1- One after the marker
// 2- One inside the marker
// 3- One before the marker
// Note that type 1 and 3 cannot exists at the same time, otherwise the
// deletion would fully include the marker (previous case)
// Part 1: Deletion after the marker
if (m.OneBasedEnd < variant.OneBasedEnd)
{
// Actually this does not affect the coordinates, so we don't care about this part
}
// Part 2: Deletion matching the marker (intersection)
long istart = Math.Max(variant.OneBasedStart, m.OneBasedStart);
long iend = Math.Min(variant.OneBasedEnd, m.OneBasedEnd);
if (iend < istart)
{
throw new ArgumentOutOfRangeException("This should never happen!");
} // Sanity check
m.OneBasedEnd -= (iend - istart + 1); // Update end coordinate
// Part 3: Deletion before the marker
if (variant.OneBasedStart < m.OneBasedEnd)
{
// Update coordinates shifting the marker to the left
long delta = m.OneBasedStart - variant.OneBasedStart;
m.OneBasedStart -= delta;
m.OneBasedEnd -= delta;
}
}
return(m);
}
/// <summary>
/// Whole exon/s deleted?
/// </summary>
private void ExonLoss()
{
foreach (Exon ex in Transcript.Exons)
{
if (Variant.Includes(ex))
{
EffectNoCodon(ex, EffectType.EXON_DELETED);
}
}
}
/// <summary>
/// How many full / partial exons does the variant affect?
/// </summary>
protected void CountAffectedExons()
{
exonFull = 0;
exonPartial = 0;
foreach (Exon ex in Transcript.Exons)
{
if (Variant.Includes(ex))
{
exonFull++;
}
else if (Variant.Intersects(ex))
{
exonPartial++;
}
}
}
public override void ChangeCodon()
{
if (Variant.Includes(Transcript))
{
// Whole transcript affected?
EffectTranscript();
}
else
{
// Does the variant affect any exons?
if (exonFull > 0 || exonPartial > 0)
{
Exons();
}
else
{
Intron();
}
}
}
public override bool CreateVariantEffect(Variant variant, VariantEffects variantEffects)
{
if (!Intersects(variant))
{
return(false);
}
if (variant.Includes(this) && variant.VarType == Variant.VariantType.DEL)
{
variantEffects.AddEffectType(variant, this, EffectType.UTR_3_DELETED); // A UTR was removed entirely
return(true);
}
Transcript tr = (Transcript)FindParent(typeof(Transcript));
long distance = utrDistance(variant, tr);
VariantEffect variantEffect = new VariantEffect(variant);
variantEffect.Set(this, EffectType.UTR_3_PRIME, EffectTypeMethods.EffectDictionary[EffectType.UTR_3_PRIME], distance >= 0 ? distance + " bases from CDS" : "");
variantEffect.Distance = distance;
variantEffects.AddEffect(variantEffect);
return(true);
}
/// <summary>
/// Analyze deletions in this transcript.
/// </summary>
/// <param name="exon"></param>
/// <returns></returns>
protected override bool ChangeCodon(Exon exon)
{
// Is there any net effect?
if (NetCodingSequenceChange == "")
{
return(false);
}
EffectType effType;
if (Variant.Includes(exon))
{
/**
* An exon has been entirely removed
*/
CodonsReference = "";
CodonsAlternate = "";
CodonStartNumber = -1;
CodonStartIndex = -1;
effType = EffectType.EXON_DELETED;
}
else if (NetCodingSequenceChange.Length % CODON_SIZE != 0)
{
/**
* Length not multiple of CODON_SIZE => FRAME_SHIFT
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Delete 'AA' pos 0: ACC CGG GAA ACC CGG GAA ACC CGG G
* Delete 'AA' pos 1: ACC CGG GAA ACC CGG GAA ACC CGG G
* Delete 'AC' pos 2: AAC CGG GAA ACC CGG GAA ACC CGG G
*/
CodonsReference = CodonsRef();
CodonsAlternate = "";
effType = EffectType.FRAME_SHIFT;
}
else if (CodonStartIndex == 0)
{
/**
* Length multiple of CODON_SIZE and insertion happens at codon boundary => CODON_DELETION
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Delete 'AAA' pos 0: CCC GGG AAA CCC GGG AAA CCC GGG
*/
CodonsReference = CodonsRef();
CodonsAlternate = "";
effType = EffectType.CODON_DELETION;
}
else
{
/**
* Length multiple of CODON_SIZE and insertion does not happen at codon boundary => CODON_CHANGE_PLUS_CODON_DELETION
* E.g. :
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Delete 'AAC' pos 1: ACC GGG AAA CCC GGG AAA CCC GGG
* Delete 'ACC' pos 2: AAC GGG AAA CCC GGG AAA CCC GGG
*/
CodonsReference = CodonsRef();
CodonsAlternate = CodonsAlt();
if (CodonsAlternate == "" || CodonsReference.StartsWith(CodonsAlternate))
{
/**
* Note: It might happen that the last codon of the exon was deleted.
* In this case there is no 'CODON_CHANGE'
* E.g.
* Original: AAA CCC GGG AAA CCC GGG AAA CCC GGG
* Delete 'GGG' pos 24: ACC CCC GGG AAA CCC GGG AAA CCC
*
* Note2: It may also be the case that the deleted bases are equal to the following ones.
* E.g.
* Original: ACG TCG TCC GGG AAA CCC GGG AAA CCC GGG
* Delete 'CGT' pos 1: ACG TCC GGG AAA CCC GGG AAA CCC GGG
*/
effType = EffectType.CODON_DELETION;
}
else
{
effType = EffectType.CODON_CHANGE_PLUS_CODON_DELETION;
}
}
Effect(exon, effType, false);
return(true);
}
/// <summary>
/// Deletion analysis using full transcript information. This is done only when the variant affects more than one exons.
/// </summary>
protected override void Exons()
{
if (exonFull == 0 && exonPartial == 1)
{
// Variant partially affects only one exon?
// => Use the standard (by exon) method
codonChangeSuper();
return;
}
else if (exonFull > 0)
{
// Full exons deleted
ExonLoss();
// Only whole exons deleted? We are done
if (exonPartial == 0)
{
return;
}
}
//---
// A combination of partial and full exons affected
//---
CodonsRefAlt();
EffectType effType;
int lenDiff = cdsAlt.Length - cdsRef.Length;
if (lenDiff % CODON_SIZE != 0)
{
effType = EffectType.FRAME_SHIFT;
}
else if (CodonStartIndex == 0)
{
effType = EffectType.CODON_DELETION;
}
else
{
if (CodonsAlternate == "" || CodonsReference.StartsWith(CodonsAlternate))
{
effType = EffectType.CODON_DELETION;
}
else
{
effType = EffectType.CODON_CHANGE_PLUS_CODON_DELETION;
}
}
// Assign to first exon
foreach (Exon ex in Transcript.Exons)
{
if (Variant.Includes(ex) || Variant.Intersects(ex))
{
Exon = ex;
break;
}
}
// Add variant effect
Effect(Exon, effType, false);
}
