protected override bool IsMatch(Target target, PeptideDocNode nodePep, out TransitionGroupDocNode nodeGroup)
{
string seqSimplified = SimplifyUnimodSequence(target.Sequence);
var seqLight = FastaSequence.StripModifications(seqSimplified, FastaSequence.RGX_HEAVY);
var seqHeavy = FastaSequence.StripModifications(seqSimplified, FastaSequence.RGX_LIGHT);
var calcLight = Settings.TryGetPrecursorCalc(IsotopeLabelType.light, nodePep.ExplicitMods);
foreach (TransitionGroupDocNode nodeGroupChild in nodePep.Children)
{
nodeGroup = nodeGroupChild;
if (nodeGroup.TransitionGroup.LabelType.IsLight)
{
// Light modifications must match.
if (!EqualsModifications(seqLight, calcLight, null))
{
return(false);
}
// If the sequence only has light modifications, a match has been found.
if (Equals(seqLight, seqSimplified))
{
return(true);
}
}
else
{
var calc = Settings.TryGetPrecursorCalc(nodeGroup.TransitionGroup.LabelType, nodePep.ExplicitMods);
if (calc != null && EqualsModifications(seqHeavy, calc, calcLight))
{
return(true);
}
}
}
nodeGroup = null;
return(false);
}
public PeptideDocNode CreateDocNodeFromSettings(string seq, Peptide peptide, SrmSettingsDiff diff,
out TransitionGroupDocNode nodeGroupMatched)
{
seq = Transition.StripChargeIndicators(seq, TransitionGroup.MIN_PRECURSOR_CHARGE, TransitionGroup.MAX_PRECURSOR_CHARGE);
if (peptide == null)
{
string seqUnmod = FastaSequence.StripModifications(seq);
try
{
peptide = new Peptide(null, seqUnmod, null, null,
Settings.PeptideSettings.Enzyme.CountCleavagePoints(seqUnmod));
}
catch (InvalidDataException)
{
nodeGroupMatched = null;
return(null);
}
}
// Use the number of modifications as the maximum, if it is less than the current
// settings to keep from over enumerating, which can be slow.
var filter = new MaxModFilter(Math.Min(seq.Count(c => c == '[' || c == '('),
Settings.PeptideSettings.Modifications.MaxVariableMods));
foreach (var nodePep in peptide.CreateDocNodes(Settings, filter))
{
var nodePepMod = CreateDocNodeFromSettings(seq, nodePep, diff, out nodeGroupMatched);
if (nodePepMod != null)
{
return(nodePepMod);
}
}
nodeGroupMatched = null;
return(null);
}
/// <summary>
/// Compares the modifications indicated in the sequence string to the calculated masses.
/// </summary>
/// <param name="seq">The modified sequence.</param>
/// <param name="calc">Calculator used to calculate the masses.</param>
/// <param name="calcLight">
/// Additional light calculator if necessary to isolate mass changes
/// caused by heavy modifications alone.
/// </param>
/// <returns>
/// True if the given calculators explain the modifications indicated on the sequence,
/// false otherwise.
/// </returns>
private bool EqualsModifications(string seq, IPrecursorMassCalc calc, IPrecursorMassCalc calcLight)
{
var modifications = Settings.PeptideSettings.Modifications;
bool structural = calcLight == null;
string aas = FastaSequence.StripModifications(seq);
foreach (var info in EnumerateSequenceInfos(seq, true))
{
int indexAA = info.IndexAA; // ReSharper
var aa = aas[indexAA];
var roundedTo = info.RoundedTo;
// If the user has indicated the modification by name, find that modification
// and calculate the mass.
double massKey;
if (info.Mass != null)
{
massKey = (double)info.Mass;
}
else
{
var info1 = info;
StaticMod modMatch = null;
int index;
if (structural &&
((index = modifications.StaticModifications.IndexOf(mod => Equals(mod.Name, info1.Name)))
!= -1))
{
modMatch = modifications.StaticModifications[index];
}
if (!structural &&
((index = modifications.HeavyModifications.IndexOf(mod => Equals(mod.Name, info1.Name)))
!= -1))
{
modMatch = modifications.HeavyModifications[index];
}
if (modMatch == null)
{
return(false);
}
roundedTo = DEFAULT_ROUNDING_DIGITS;
massKey = Math.Round(GetDefaultModMass(aa, modMatch), roundedTo);
}
double massMod = Math.Round(calc.GetAAModMass(aas[indexAA], indexAA, aas.Length), roundedTo);
// Subtract the mass difference of the light
// modifications to isolate the masses of the heavy modifications.
if (calcLight != null)
{
massMod -= Math.Round(calcLight.GetAAModMass(aas[indexAA], indexAA, aas.Length), roundedTo);
}
if (!Equals(massKey, massMod))
{
return(false);
}
}
return(true);
}
public string SimplifyUnimodSequence(string seq)
{
var sb = new StringBuilder(seq);
string aas = FastaSequence.StripModifications(seq);
int indexAA = 0;
int i = 0;
while (i < seq.Length)
{
var aa = aas[indexAA];
int indexBracket = i + 1;
if (indexBracket < seq.Length && (FastaSequence.OPEN_MOD.Contains(seq[indexBracket])))
{
char openBracket = seq[indexBracket];
char closeBracket = FastaSequence.CLOSE_MOD[FastaSequence.OPEN_MOD.IndexOf(c => c == openBracket)];
int indexStart = indexBracket + 1;
int indexClose = seq.IndexOf(closeBracket, indexBracket);
string mod = seq.Substring(indexStart, indexClose - indexStart);
i = indexClose;
ModTerminus?modTerminus = null;
if (indexAA == 0)
{
modTerminus = ModTerminus.N;
}
if (indexAA == aas.Length - 1)
{
modTerminus = ModTerminus.C;
}
// Here we are only interested in uniMod
int uniModId;
if (TryGetIdFromUnimod(mod, out uniModId))
{
var staticMod = GetStaticMod(uniModId, aa, modTerminus);
if (staticMod == null)
{
ThrowUnimodException(seq, uniModId, indexAA, indexBracket, indexClose);
return(null); // Keep ReSharper happy
}
string name = staticMod.Name;
bool isHeavy = !UniMod.DictStructuralModNames.ContainsKey(name);
sb[indexBracket] = isHeavy ? '{' : '[';
sb[indexClose] = isHeavy ? '}' : ']';
}
}
// If the next character is a bracket, continue using the same amino
// acid and leave i where it is.
int iNext = i + 1;
if (iNext >= seq.Length || !FastaSequence.OPEN_MOD.Contains(seq[iNext]))
{
indexAA++;
i++;
}
}
return(sb.ToString());
}
public PeptideDocNode GetModifiedNode(string seq, FastaSequence fastaSequence)
{
var seqUnmod = FastaSequence.StripModifications(seq);
var peptide = fastaSequence != null
? fastaSequence.CreateFullPeptideDocNode(Settings, new Target(seqUnmod)).Peptide
: new Peptide(null, seqUnmod, null, null,
Settings.PeptideSettings.Enzyme.CountCleavagePoints(seqUnmod));
// First, try to create the peptide using the current settings.
TransitionGroupDocNode nodeGroup;
PeptideDocNode nodePep =
CreateDocNodeFromSettings(new Target(seq), peptide, SrmSettingsDiff.ALL, out nodeGroup);
if (nodePep != null)
{
return(nodePep);
}
// Create the peptideDocNode.
nodePep = fastaSequence == null
? new PeptideDocNode(peptide)
: fastaSequence.CreateFullPeptideDocNode(Settings, new Target(seqUnmod));
return(CreateDocNodeFromMatches(nodePep, EnumerateSequenceInfos(seq, false)));
}
private IEnumerable <AAModInfo> EnumerateSequenceInfos(string seq, bool includeUnmod)
{
string aas = FastaSequence.StripModifications(seq);
bool isSpecificHeavy = FastaSequence.OPEN_MOD.All(paren => aas.Length > seq.Count(c => c == paren));
int indexAA = 0;
int indexAAInSeq = 0;
int i = 0;
while (i < seq.Length)
{
var aa = aas[indexAA];
int indexBracket = i + 1;
if (indexBracket < seq.Length && (FastaSequence.OPEN_MOD.Contains(seq[indexBracket])))
{
char openBracket = seq[indexBracket];
bool isHeavy = openBracket == '{';
char closeBracket = FastaSequence.CLOSE_MOD[FastaSequence.OPEN_MOD.IndexOf(c => c == openBracket)];
int indexStart = indexBracket + 1;
int indexClose = seq.IndexOf(closeBracket, indexBracket);
string mod = seq.Substring(indexStart, indexClose - indexStart);
i = indexClose;
ModTerminus?modTerminus = null;
if (indexAA == 0)
{
modTerminus = ModTerminus.N;
}
if (indexAA == aas.Length - 1)
{
modTerminus = ModTerminus.C;
}
string name = null;
double?mass = null;
int roundedTo = 0;
// If passed in modification in UniMod notation, look up the id and find the name and mass
int uniModId;
if (TryGetIdFromUnimod(mod, out uniModId))
{
var staticMod = GetStaticMod(uniModId, aa, modTerminus);
if (staticMod == null)
{
throw ThrowUnimodException(seq, uniModId, indexAA, indexBracket, indexClose);
}
name = staticMod.Name;
isHeavy = !UniMod.IsStructuralModification(name);
// CONSIDER: Mass depends on TransitionPrediction settings for precursors
mass = staticMod.MonoisotopicMass;
roundedTo = DEFAULT_ROUNDING_DIGITS;
}
else
{
MassModification massModification = MassModification.Parse(mod);
if (massModification != null)
{
mass = massModification.Mass;
roundedTo = Math.Min(massModification.Precision, DEFAULT_ROUNDING_DIGITS);
}
else
{
name = mod;
}
}
if (mass.HasValue)
{
mass = Math.Round(mass.Value, roundedTo);
}
var key = new AAModKey
{
Name = name,
Mass = mass,
AA = aa,
Terminus = modTerminus,
UserIndicatedHeavy = isHeavy,
RoundedTo = roundedTo,
AppearsToBeSpecificMod = isSpecificHeavy
};
yield return(new AAModInfo
{
ModKey = key,
IndexAA = indexAA,
IndexAAInSeq = indexAAInSeq,
});
}
else if (includeUnmod)
{
// If need unmodified amino acids (as when
// checking for equality), yield SequenceKeys for these AA's.
var key = new AAModKey
{
AA = aa,
Mass = 0
};
yield return(new AAModInfo
{
ModKey = key,
IndexAA = indexAA,
});
}
// If the next character is a bracket, continue using the same amino
// acid and leave i where it is.
int iNext = i + 1;
if (iNext >= seq.Length || !FastaSequence.OPEN_MOD.Contains(seq[iNext]))
{
i = indexAAInSeq = iNext;
indexAA++;
}
}
}
