private bool CanAddLabelType(IsotopeLabelType labelType)
{
if (_settings.TryGetPrecursorCalc(labelType, null) != null)
{
return(true);
}
return(_document.Molecules.Any(nodePep =>
_settings.TryGetPrecursorCalc(labelType, nodePep.ExplicitMods) != null));
}
private static IEnumerable <KeyValuePair <IsotopeLabelType, string> > GetTypedModifiedSequences(
PeptideDocNode nodePep, SrmSettings settings)
{
foreach (var labelType in settings.PeptideSettings.Modifications.GetModificationTypes())
{
if (nodePep.Peptide.IsCustomMolecule)
{
continue;
}
// Only return the modified sequence, if the peptide actually as a child
// of this type.
if (!nodePep.HasChildType(labelType))
{
continue;
}
var calc = settings.TryGetPrecursorCalc(labelType, nodePep.ExplicitMods);
if (calc == null)
{
continue;
}
string modSequence = calc.GetModifiedSequence(nodePep.Peptide.Target, true).Sequence; // Never have to worry about this being a custom molecule, we already checked
// Only return if the modified sequence contains modifications
if (modSequence.Contains('['))
{
yield return(new KeyValuePair <IsotopeLabelType, string>(labelType, modSequence));
}
}
}
/// <summary>
/// Creates a text sequence with the fully modified peptide sequence text
/// and font information for a given label type.
/// </summary>
private static TextSequence CreateTypeTextSequence(PeptideDocNode nodePep, SrmSettings settings,
IsotopeLabelType labelType, ModFontHolder fonts)
{
var calc = settings.TryGetPrecursorCalc(labelType, nodePep.ExplicitMods);
if (calc == null)
{
return(null);
}
return(new TextSequence
{
Text = nodePep.IsProteomic
? calc.GetModifiedSequence(nodePep.Peptide.Target, SequenceModFormatType.mass_diff_narrow, false).Sequence
: nodePep.CustomMolecule.DisplayName,
Font = fonts.GetModFont(labelType),
Color = ModFontHolder.GetModColor(labelType)
});
}
/// <summary>
/// Creates a text sequence with the fully modified peptide sequence text
/// and font information for a given label type.
/// </summary>
private static TextSequence CreateTypeTextSequence(PeptideDocNode nodePep, SrmSettings settings,
IsotopeLabelType labelType, ModFontHolder fonts)
{
var calc = settings.TryGetPrecursorCalc(labelType, nodePep.ExplicitMods);
if (calc == null)
{
return(null);
}
return(new TextSequence
{
Text = nodePep.IsProteomic
? calc.GetModifiedSequence(nodePep.Peptide.Sequence, true)
: nodePep.CustomIon.DisplayName,
Font = fonts.GetModFont(labelType),
Color = ModFontHolder.GetModColor(labelType)
});
}
public IEnumerable <TransitionDocNode> GetTransitions(SrmSettings settings,
TransitionGroupDocNode groupDocNode,
ExplicitMods mods,
double precursorMz,
IsotopeDistInfo isotopeDist,
SpectrumHeaderInfo libInfo,
IDictionary <double, LibraryRankedSpectrumInfo.RankedMI> transitionRanks,
bool useFilter)
{
Assume.IsTrue(ReferenceEquals(groupDocNode.TransitionGroup, this));
// Get necessary mass calculators and masses
var calcFilterPre = settings.GetPrecursorCalc(IsotopeLabelType.light, mods);
var calcPredictPre = settings.TryGetPrecursorCalc(LabelType, mods) ?? calcFilterPre;
var calcFilter = settings.GetFragmentCalc(IsotopeLabelType.light, mods);
var calcPredict = settings.GetFragmentCalc(LabelType, mods);
var sequence = Peptide.Target;
// Save the true precursor m/z for TranstionSettings.Accept() now that all isotope types are
// checked. This is more correct than just using the light precursor m/z for precursor window
// exclusion.
double precursorMzAccept = precursorMz;
if (!ReferenceEquals(calcFilter, calcPredict))
{
// Get the normal precursor m/z for filtering, so that light and heavy ion picks will match.
var adduct = groupDocNode.TransitionGroup.PrecursorAdduct;
string isotopicFormula;
precursorMz = IsCustomIon ?
adduct.MzFromNeutralMass(calcFilterPre.GetPrecursorMass(groupDocNode.CustomMolecule, null, Adduct.EMPTY, out isotopicFormula),
calcFilterPre.MassType.IsMonoisotopic() ? MassType.Monoisotopic : MassType.Average) : // Don't pass the isMassH bit
SequenceMassCalc.GetMZ(calcFilterPre.GetPrecursorMass(sequence), adduct);
}
if (!IsAvoidMismatchedIsotopeTransitions)
{
precursorMzAccept = precursorMz;
}
var tranSettings = settings.TransitionSettings;
var filter = tranSettings.Filter;
var adducts = groupDocNode.IsCustomIon ? filter.SmallMoleculeFragmentAdducts : filter.PeptideProductCharges;
var startFinder = filter.FragmentRangeFirst;
var endFinder = filter.FragmentRangeLast;
double precursorMzWindow = filter.PrecursorMzWindow;
var types = groupDocNode.IsCustomIon ? filter.SmallMoleculeIonTypes : filter.PeptideIonTypes;
MassType massType = tranSettings.Prediction.FragmentMassType;
int minMz = tranSettings.Instrument.GetMinMz(precursorMzAccept);
int maxMz = tranSettings.Instrument.MaxMz;
var pepMods = settings.PeptideSettings.Modifications;
var potentialLosses = CalcPotentialLosses(sequence, pepMods, mods, massType);
// A start m/z will need to be calculated if the start fragment
// finder uses m/z and their are losses to consider. If the filter
// is set to only consider fragments with m/z greater than the
// precursor, the code below needs to also prevent loss fragments
// from being under that m/z.
double startMz = 0;
// Get library settings
var pick = tranSettings.Libraries.Pick;
if (!useFilter)
{
pick = TransitionLibraryPick.all;
var listAll = IsProteomic
? Transition.DEFAULT_PEPTIDE_CHARGES.ToList()
: Transition.DEFAULT_MOLECULE_CHARGES.ToList();
listAll.AddRange(adducts.Where(c => !listAll.Contains(c)));
listAll.Sort();
adducts = listAll.ToArray();
types = IsProteomic ? Transition.PEPTIDE_ION_TYPES : Transition.MOLECULE_ION_TYPES;
}
// If there are no libraries or no library information, then
// picking cannot use library information
else if (!settings.PeptideSettings.Libraries.HasLibraries || libInfo == null)
{
pick = TransitionLibraryPick.none;
}
// If filtering without library picking
if (potentialLosses != null && IsProteomic)
{
if (pick == TransitionLibraryPick.none)
{
// Only include loss combinations where all losses are included always
potentialLosses = potentialLosses.Where(losses =>
losses.All(loss => loss.TransitionLoss.Loss.Inclusion == LossInclusion.Always)).ToArray();
}
else if (useFilter)
{
// Exclude all losses which should never be included by default
potentialLosses = potentialLosses.Where(losses =>
losses.All(loss => loss.TransitionLoss.Loss.Inclusion != LossInclusion.Never)).ToArray();
}
if (!potentialLosses.Any())
{
potentialLosses = null;
}
}
// Return precursor ions
if (!useFilter || types.Contains(IonType.precursor))
{
bool libraryFilter = (pick == TransitionLibraryPick.all || pick == TransitionLibraryPick.filter);
foreach (var nodeTran in GetPrecursorTransitions(settings, mods, calcPredictPre, calcPredict ?? calcFilter,
precursorMz, isotopeDist, potentialLosses, transitionRanks, libraryFilter, useFilter))
{
if (minMz <= nodeTran.Mz && nodeTran.Mz <= maxMz)
{
yield return(nodeTran);
}
}
}
// Return special ions from settings, if this is a peptide
if (!IsCustomIon)
{
// This is a peptide, but it may have custom transitions (reporter ions), check those
foreach (var measuredIon in tranSettings.Filter.MeasuredIons.Where(m => m.IsCustom))
{
if (useFilter && measuredIon.IsOptional)
{
continue;
}
var tran = new Transition(this, measuredIon.Adduct, null, measuredIon.SettingsCustomIon);
var mass = settings.GetFragmentMass(null, null, tran, null);
var nodeTran = new TransitionDocNode(tran, null, mass, TransitionDocNode.TransitionQuantInfo.DEFAULT);
if (minMz <= nodeTran.Mz && nodeTran.Mz <= maxMz)
{
yield return(nodeTran);
}
}
}
// For small molecules we can't generate new nodes, so just mz filter those we have
foreach (var nodeTran in groupDocNode.Transitions.Where(tran => tran.Transition.IsNonPrecursorNonReporterCustomIon()))
{
if (minMz <= nodeTran.Mz && nodeTran.Mz <= maxMz)
{
yield return(nodeTran);
}
}
if (!sequence.IsProteomic) // Completely custom CONSIDER(bspratt) can this be further extended for small mol libs?
{
yield break;
}
// If picking relies on library information
if (useFilter && pick != TransitionLibraryPick.none)
{
// If it is not yet loaded, or nothing got ranked, return an empty enumeration
if (!settings.PeptideSettings.Libraries.IsLoaded ||
(transitionRanks != null && transitionRanks.Count == 0))
{
yield break;
}
}
var massesPredict = calcPredict.GetFragmentIonMasses(sequence);
int len = massesPredict.GetLength(1);
if (len == 0)
{
yield break;
}
var massesFilter = massesPredict;
if (!ReferenceEquals(calcFilter, calcPredict))
{
// Get the normal m/z values for filtering, so that light and heavy
// ion picks will match.
massesFilter = calcFilter.GetFragmentIonMasses(sequence);
}
// Get types other than this to make sure matches are possible for all types
var listOtherTypes = new List <Tuple <TransitionGroupDocNode, IFragmentMassCalc> >();
foreach (var labelType in settings.PeptideSettings.Modifications.GetModificationTypes())
{
if (Equals(labelType, LabelType))
{
continue;
}
var calc = settings.GetFragmentCalc(labelType, mods);
if (calc == null)
{
continue;
}
var tranGroupOther = new TransitionGroup(Peptide, PrecursorAdduct, labelType, false, DecoyMassShift);
var nodeGroupOther = new TransitionGroupDocNode(tranGroupOther, Annotations.EMPTY, settings, mods,
libInfo, ExplicitTransitionGroupValues.EMPTY, null, new TransitionDocNode[0], false);
listOtherTypes.Add(new Tuple <TransitionGroupDocNode, IFragmentMassCalc>(nodeGroupOther, calc));
}
// Loop over potential product ions picking transitions
foreach (IonType type in types)
{
// Precursor type is handled above.
if (type == IonType.precursor)
{
continue;
}
foreach (var adduct in adducts)
{
// Precursor charge can never be lower than product ion charge.
if (Math.Abs(PrecursorAdduct.AdductCharge) < Math.Abs(adduct.AdductCharge))
{
continue;
}
int start = 0, end = 0;
if (pick != TransitionLibraryPick.all)
{
start = startFinder.FindStartFragment(massesFilter, type, adduct,
precursorMz, precursorMzWindow, out startMz);
end = endFinder.FindEndFragment(type, start, len);
if (Transition.IsCTerminal(type))
{
Helpers.Swap(ref start, ref end);
}
}
for (int i = 0; i < len; i++)
{
// Get the predicted m/z that would be used in the transition
var massH = massesPredict[type, i];
Assume.IsTrue(massH.IsMassH());
Assume.IsTrue(massH.IsMonoIsotopic() == calcPredict.MassType.IsMonoisotopic());
foreach (var losses in CalcTransitionLosses(type, i, massType, potentialLosses))
{
double ionMz = SequenceMassCalc.GetMZ(Transition.CalcMass(massH, losses), adduct);
// Make sure the fragment m/z value falls within the valid instrument range.
// CONSIDER: This means that a heavy transition might excede the instrument
// range where a light one is accepted, leading to a disparity
// between heavy and light transtions picked.
if (minMz > ionMz || ionMz > maxMz)
{
continue;
}
TransitionDocNode nodeTranReturn = null;
bool accept = true;
if (pick == TransitionLibraryPick.all || pick == TransitionLibraryPick.all_plus)
{
if (!useFilter)
{
nodeTranReturn = CreateTransitionNode(type, i, adduct, massH, losses, transitionRanks);
accept = false;
}
else
{
if (IsMatched(transitionRanks, ionMz, type, adduct, losses))
{
nodeTranReturn = CreateTransitionNode(type, i, adduct, massH, losses, transitionRanks);
accept = false;
}
// If allowing library or filter, check the filter to decide whether to accept
else if (pick == TransitionLibraryPick.all_plus &&
tranSettings.Accept(sequence, precursorMzAccept, type, i, ionMz, start, end, startMz))
{
nodeTranReturn = CreateTransitionNode(type, i, adduct, massH, losses, transitionRanks);
}
}
}
else if (tranSettings.Accept(sequence, precursorMzAccept, type, i, ionMz, start, end, startMz))
{
if (pick == TransitionLibraryPick.none)
{
nodeTranReturn = CreateTransitionNode(type, i, adduct, massH, losses, transitionRanks);
}
else
{
if (IsMatched(transitionRanks, ionMz, type, adduct, losses))
{
nodeTranReturn = CreateTransitionNode(type, i, adduct, massH, losses, transitionRanks);
}
}
}
if (nodeTranReturn != null)
{
if (IsAvoidMismatchedIsotopeTransitions &&
!OtherLabelTypesAllowed(settings, minMz, maxMz, start, end, startMz, accept,
groupDocNode, nodeTranReturn, listOtherTypes))
{
continue;
}
Assume.IsTrue(minMz <= nodeTranReturn.Mz && nodeTranReturn.Mz <= maxMz);
yield return(nodeTranReturn);
}
}
}
}
}
}