public bool HasPrecursorCalc(IsotopeLabelType labelType, ExplicitMods mods)
{
if (labelType.IsLight)
return true;
return TryGetPrecursorCalc(labelType, mods) != null;
}
public double[] GetRetentionTimes(MsDataFileUri filePath, string peptideSequence, ExplicitMods explicitMods,
RetentionTimeAlignmentIndex alignmentIndex = null)
{
string basename = filePath.GetFileNameWithoutExtension();
var source = DocumentRetentionTimes.RetentionTimeSources.Find(basename);
if (source == null)
{
return new double[0];
}
var library = PeptideSettings.Libraries.GetLibrary(source.Library);
if (library == null)
{
return new double[0];
}
var modifiedSequences = GetTypedSequences(peptideSequence, explicitMods)
.Select(typedSequence => typedSequence.ModifiedSequence);
int? index = (alignmentIndex != null ? alignmentIndex.FileIndex : null);
var times = library.GetRetentionTimesWithSequences(source.Name, modifiedSequences, ref index).ToArray();
if (alignmentIndex != null)
alignmentIndex.FileIndex = index;
return times;
}
public void OkDialog()
{
var peptide = NodePeptide.Peptide;
var explicitModsCurrent = NodePeptide.ExplicitMods;
var modsDoc = DocSettings.PeptideSettings.Modifications;
var implicitMods = new ExplicitMods(NodePeptide,
modsDoc.StaticModifications, Settings.Default.StaticModList,
modsDoc.GetHeavyModifications(), Settings.Default.HeavyModList);
// Get static modifications from the dialog, and check for equality with
// the document implicit modifications.
TypedExplicitModifications staticTypedMods = null;
bool isVariableStaticMods = false;
var staticMods = GetExplicitMods(_listComboStatic, Settings.Default.StaticModList);
if (ArrayUtil.EqualsDeep(staticMods, implicitMods.StaticModifications))
{
if (!NodePeptide.HasVariableMods)
staticMods = null; // Use implicit modifications
else
{
staticMods = explicitModsCurrent.StaticModifications;
isVariableStaticMods = true;
}
}
else if (explicitModsCurrent != null &&
ArrayUtil.EqualsDeep(staticMods, explicitModsCurrent.StaticModifications))
{
staticMods = explicitModsCurrent.StaticModifications;
}
if (staticMods != null)
{
staticTypedMods = new TypedExplicitModifications(peptide,
IsotopeLabelType.light, staticMods);
}
var listHeavyTypedMods = new List<TypedExplicitModifications>();
for (int i = 0; i < _listLabelTypeHeavy.Count; i++)
{
var labelType = _listLabelTypeHeavy[i];
var heavyMods = GetExplicitMods(_listListComboHeavy[i], Settings.Default.HeavyModList);
if (ArrayUtil.EqualsDeep(heavyMods, implicitMods.GetModifications(labelType)))
continue;
var heavyTypedMods = new TypedExplicitModifications(peptide, labelType, heavyMods);
listHeavyTypedMods.Add(heavyTypedMods.AddModMasses(staticTypedMods));
}
ExplicitMods explicitMods = null;
if (staticMods != null || listHeavyTypedMods.Count > 0)
explicitMods = new ExplicitMods(peptide, staticMods, listHeavyTypedMods, isVariableStaticMods);
Helpers.AssignIfEquals(ref explicitMods, explicitModsCurrent);
ExplicitMods = explicitMods;
DialogResult = DialogResult.OK;
Close();
}
public double GetPrecursorMass(IsotopeLabelType labelType, string seq, ExplicitMods mods)
{
return GetPrecursorCalc(labelType, mods).GetPrecursorMass(seq);
}
public RelativeRT GetRelativeRT(IsotopeLabelType labelType, string seq, ExplicitMods mods)
{
if (labelType.IsLight)
return RelativeRT.Matching;
// Default is matching
RelativeRT relativeRT = RelativeRT.Matching;
// One unkown modification makes everything unknown
// One preceding modification with no unknowns make relative RT preceding
// Overlapping overrides matching
if (mods != null && mods.IsModified(labelType))
{
foreach (var mod in mods.GetModifications(labelType))
{
if (mod.Modification.RelativeRT == RelativeRT.Unknown)
return RelativeRT.Unknown;
if (mod.Modification.RelativeRT == RelativeRT.Preceding)
relativeRT = RelativeRT.Preceding;
else if (mod.Modification.RelativeRT == RelativeRT.Overlapping &&
relativeRT == RelativeRT.Matching)
relativeRT = RelativeRT.Overlapping;
}
}
else
{
foreach (var mod in PeptideSettings.Modifications.GetModifications(labelType))
{
if (!mod.IsMod(seq))
continue;
if (mod.RelativeRT == RelativeRT.Unknown)
return RelativeRT.Unknown;
if (mod.RelativeRT == RelativeRT.Preceding)
relativeRT = RelativeRT.Preceding;
else if (mod.RelativeRT == RelativeRT.Overlapping &&
relativeRT == RelativeRT.Matching)
relativeRT = RelativeRT.Overlapping;
}
}
return relativeRT;
}
public IFragmentMassCalc GetFragmentCalc(IsotopeLabelType labelType, ExplicitMods mods)
{
var massCalcBase = GetBaseCalc(labelType, mods, _fragmentMassCalcs);
if (massCalcBase != null)
{
// If this type is not explicitly modified, then it must be
// heavy with explicit light modifications.
if (!mods.IsModified(labelType))
labelType = IsotopeLabelType.light;
if (!labelType.IsLight && !mods.HasModifications(labelType))
return null;
return new ExplicitSequenceMassCalc(mods, massCalcBase, labelType);
}
return GetMassCalc(labelType, _fragmentMassCalcs);
}
public string GetModifiedSequence(string seq,
IsotopeLabelType labelType,
ExplicitMods mods,
SequenceModFormatType format = SequenceModFormatType.mass_diff,
bool useExplicitModsOnly = false)
{
return GetPrecursorCalc(labelType, mods).GetModifiedSequence(seq, format, useExplicitModsOnly);
}
private bool Accept(SrmSettings settings,
Peptide peptide,
ExplicitMods mods,
IList<int> precursorCharges,
PeptideFilterType filterType,
out bool allowVariableMods)
{
// Assume variable modifications are not allowed until proven otherwise
allowVariableMods = false;
// Only filter user specified peptides based on the heuristic
// filter when explicitly requested.
bool useFilter = filterType == PeptideFilterType.full;
if (filterType == PeptideFilterType.fasta)
useFilter = peptide.Begin.HasValue;
var libraries = PeptideSettings.Libraries;
if (!libraries.HasLibraries || libraries.Pick == PeptidePick.filter)
{
if (!useFilter)
{
allowVariableMods = true;
return true;
}
return PeptideSettings.Filter.Accept(settings, peptide, mods, out allowVariableMods);
}
// Check if the peptide is in the library for one of the
// acceptable precursor charges.
bool inLibrary = false;
// If the libraries are not fully loaded, then act like nothing
// could be found in the libraries. This will be corrected when
// the libraries are loaded.
if (libraries.IsLoaded &&
// Only check the library, if this is a custom ion or a peptide that already has
// a variable modification, or the library contains some form of the peptide.
// This is a performance improvement over checking every variable modification
// of a peptide when it is not even in the library.
(peptide.IsCustomIon || (mods != null && mods.IsVariableStaticMods) || LibrariesContainAny(peptide.Sequence)))
{
// Only allow variable modifications, if the peptide has no modifications
// or already checking variable modifications, and there is reason to check
// the library. Failing to do this check profiled as a performance bottleneck.
allowVariableMods = mods == null || mods.IsVariableStaticMods;
inLibrary = LibrariesContainMeasurablePeptide(peptide, precursorCharges, mods);
}
switch (libraries.Pick)
{
case PeptidePick.library:
return inLibrary;
case PeptidePick.both:
return inLibrary && (!useFilter || PeptideSettings.Filter.Accept(settings, peptide, mods, out allowVariableMods));
default:
return inLibrary || (!useFilter || PeptideSettings.Filter.Accept(settings, peptide, mods, out allowVariableMods));
}
}
private IEnumerable<IsotopeLabelType> GetHeavyLabelTypes(ExplicitMods mods)
{
foreach (var typedMods in PeptideSettings.Modifications.GetHeavyModifications())
{
IsotopeLabelType labelType = typedMods.LabelType;
if (HasPrecursorCalc(labelType, mods))
yield return labelType;
}
}
public bool TryLoadSpectrum(string sequence, int charge, ExplicitMods mods,
out IsotopeLabelType type, out SpectrumPeaksInfo spectrum)
{
var libraries = PeptideSettings.Libraries;
foreach (var typedSequence in GetTypedSequences(sequence, mods))
{
var key = new LibKey(typedSequence.ModifiedSequence, charge);
if (libraries.TryLoadSpectrum(key, out spectrum))
{
type = typedSequence.LabelType;
return true;
}
}
type = IsotopeLabelType.light;
spectrum = null;
return false;
}
private static SequenceMassCalc GetBaseCalc(IsotopeLabelType labelType,
ExplicitMods mods, IList<TypedMassCalc> massCalcs)
{
if (mods == null)
return null;
var calcLightImplicit = massCalcs[0].MassCalc;
// If the light type is not modified
if (!mods.IsModified(IsotopeLabelType.light))
{
// If requesting the light calculator or an unmodified heavy,
// then no explicit calculator is required.
if (labelType.IsLight || !mods.IsModified(labelType))
return null;
// Otherwise, use its calculator as the base for a heavy type
// to make sure the implicit light modifications are included.
return calcLightImplicit;
}
// If the type requested is not modified, it must be a heavy type
// with the light type modified. In this case, return the heavy
// calculator as the base, to which the light explicit modifications
// may be applied to get modified masses.
if (!mods.IsModified(labelType))
return GetMassCalc(labelType, massCalcs);
// If the light modifications are variable, and this is a type for
// which explicit modifications exist (including the light type itself),
// then return the light calculator as base.
if (mods.IsVariableStaticMods)
return calcLightImplicit;
// If both light and this type are modified, then us a base calculator
// that contains no modifications at all.
return (calcLightImplicit.MassType == MassType.Monoisotopic ?
MonoisotopicMassCalc : AverageMassCalc);
}
public bool TryGetRetentionTimes(string sequence, int charge, ExplicitMods mods, MsDataFileUri filePath,
out IsotopeLabelType type, out double[] retentionTimes)
{
var libraries = PeptideSettings.Libraries;
foreach (var typedSequence in GetTypedSequences(sequence, mods))
{
var key = new LibKey(typedSequence.ModifiedSequence, charge);
if (libraries.TryGetRetentionTimes(key, filePath, out retentionTimes))
{
type = typedSequence.LabelType;
return true;
}
}
type = IsotopeLabelType.light;
retentionTimes = null;
return false;
}
public bool TryGetLibInfo(string sequence, int charge, ExplicitMods mods,
out IsotopeLabelType type, out SpectrumHeaderInfo libInfo)
{
if (sequence == null)
{
type = null;
libInfo = null;
return false;
}
var libraries = PeptideSettings.Libraries;
foreach (var typedSequence in GetTypedSequences(sequence, mods))
{
var key = new LibKey(typedSequence.ModifiedSequence, charge);
if (libraries.TryGetLibInfo(key, out libInfo))
{
type = typedSequence.LabelType;
return true;
}
}
type = IsotopeLabelType.light;
libInfo = null;
return false;
}
public bool LibrariesContainMeasurablePeptide(Peptide peptide, IList<int> precursorCharges, ExplicitMods mods)
{
if (LibrariesContainMeasurablePeptide(peptide, IsotopeLabelType.light, precursorCharges, mods))
return true;
// If light version not found, try heavy
foreach (var labelType in GetHeavyLabelTypes(mods))
{
if (LibrariesContainMeasurablePeptide(peptide, labelType, precursorCharges, mods))
return true;
}
return false;
}
public double[] GetAllRetentionTimes(MsDataFileUri filePath, string peptideSequence, ExplicitMods explicitMods)
{
var times = new List<double>();
times.AddRange(GetRetentionTimes(filePath, peptideSequence, explicitMods));
times.AddRange(GetAlignedRetentionTimes(filePath, peptideSequence, explicitMods));
return times.ToArray();
}
private IEnumerable<TypedSequence> GetTypedSequences(string sequence, ExplicitMods mods)
{
var labelType = IsotopeLabelType.light;
string modifiedSequence = GetModifiedSequence(sequence, labelType, mods);
yield return new TypedSequence(modifiedSequence, labelType);
foreach (var labelTypeHeavy in GetHeavyLabelTypes(mods))
{
modifiedSequence = GetModifiedSequence(sequence, labelTypeHeavy, mods);
yield return new TypedSequence(modifiedSequence, labelTypeHeavy);
}
}
/// <summary>
/// Loads a list of all non-redundant spectra found in all loaded libraries
/// matching the criteria passed in.
/// </summary>
/// <param name="sequence"> The sequence to match. </param>
/// <param name="charge"> The charge to match. </param>
/// <param name="mods"> The modifications to match. </param>
/// <returns> Returns a list of the matching spectra. </returns>
public IEnumerable<SpectrumInfo> GetBestSpectra(string sequence, int charge, ExplicitMods mods)
{
var libraries = PeptideSettings.Libraries;
return from typedSequence in GetTypedSequences(sequence, mods)
let key = new LibKey(typedSequence.ModifiedSequence, charge)
from spectrumInfo in libraries.GetSpectra(key, typedSequence.LabelType, true)
select spectrumInfo;
}
private bool LibrariesContainMeasurablePeptide(Peptide peptide, IsotopeLabelType labelType,
IEnumerable<int> precursorCharges, ExplicitMods mods)
{
string sequenceMod = GetModifiedSequence(peptide.Sequence, labelType, mods);
foreach (int charge in precursorCharges)
{
if (LibrariesContain(sequenceMod, charge))
{
// Make sure the peptide for the found spectrum is measurable on
// the current instrument.
double precursorMass = GetPrecursorMass(labelType, peptide.Sequence, mods);
if (IsMeasurable(precursorMass, charge))
return true;
}
}
return false;
}
public double GetFragmentMass(IsotopeLabelType labelType, ExplicitMods mods,
Transition transition, IsotopeDistInfo isotopeDist)
{
// Return the singly protonated mass of the peptide fragment, or custom ion mass before electron removal
IFragmentMassCalc calc = GetFragmentCalc(labelType, mods);
if (calc == null && transition.IsCustom())
{
// Small molecules provide their own ion formula, just use the standard calculator
calc = GetDefaultFragmentCalc();
}
if (calc == null)
{
Assume.Fail(string.Format("Unable to locate fragment calculator for isotope label type {0} and mods {1}", // Not L10N
labelType == null ? "(null)" : labelType.ToString(), // Not L10N
mods == null ? "(null)" : mods.ToString())); // Not L10N
return 0; // Keep resharper happy
}
return calc.GetFragmentMass(transition, isotopeDist);
}
public bool Accept(SrmSettings settings, Peptide peptide, ExplicitMods explicitMods, out bool allowVariableMods)
{
return Accept(settings,
peptide,
explicitMods,
TransitionSettings.Filter.PrecursorCharges,
PeptideFilterType.fasta,
out allowVariableMods);
}
public IPrecursorMassCalc GetPrecursorCalc(IsotopeLabelType labelType, ExplicitMods mods)
{
var precursorCalc = TryGetPrecursorCalc(labelType, mods);
if (precursorCalc == null)
{
// Try to track down this exception:
// https://skyline.gs.washington.edu/labkey/announcements/home/issues/exceptions/thread.view?entityId=217d79c8-9a84-1032-ae5f-da2025829168&_anchor=19667#row:19667
throw new InvalidDataException(
String.Format("unable to locate precursor calculator for isotope label type {0} and mods {1}", // Not L10N
labelType == null ? "(null)" : labelType.ToString(), // Not L10N
mods == null ? "(null)" : mods.ToString())); // Not L10N
}
return precursorCalc;
}
/// <summary>
/// This version of Accept is used to select transition groups after the peptide
/// itself has already been screened. For this reason, it only applies library
/// filtering.
/// </summary>
public bool Accept(SrmSettings settings, Peptide peptide, ExplicitMods mods, int charge)
{
bool allowVariableMods;
return Accept(settings, peptide, mods, new[] { charge }, PeptideFilterType.library, out allowVariableMods);
}
/// <summary>
/// Loads a list of all the spectra found in all loaded libraries
/// matching the criteria passed in.
/// </summary>
/// <param name="sequence"> The sequence to match. </param>
/// <param name="charge"> The charge to match. </param>
/// <param name="labelType">The primary label type to match</param>
/// <param name="mods"> The modifications to match. </param>
/// <returns> Returns a list of the matching spectra. </returns>
public IEnumerable<SpectrumInfo> GetRedundantSpectra(string sequence, int charge, IsotopeLabelType labelType,
ExplicitMods mods)
{
string sequenceMod = GetModifiedSequence(sequence, labelType, mods);
return PeptideSettings.Libraries.GetSpectra(new LibKey(sequenceMod, charge), labelType, false);
}
public double[] GetAlignedRetentionTimes(MsDataFileUri filePath, string peptideSequence, ExplicitMods explicitMods)
{
string basename = filePath.GetFileNameWithoutExtension();
var fileAlignments = DocumentRetentionTimes.FileAlignments.Find(basename);
return GetAlignedRetentionTimes(new RetentionTimeAlignmentIndices(fileAlignments), peptideSequence, explicitMods);
}
public double[] GetRetentionTimes(string filePath, string peptideSequence, ExplicitMods explicitMods,
RetentionTimeAlignmentIndex alignmentIndex = null)
{
return GetRetentionTimes(MsDataFileUri.Parse(filePath), peptideSequence, explicitMods, alignmentIndex);
}
public double[] GetAlignedRetentionTimes(RetentionTimeAlignmentIndices alignmentIndices, string peptideSequence, ExplicitMods explicitMods)
{
var times = new List<double>();
if (alignmentIndices != null)
{
foreach (var alignmentIndex in alignmentIndices)
{
var unalignedTimes = GetRetentionTimes(MsDataFileUri.Parse(alignmentIndex.Alignment.Name), peptideSequence, explicitMods, alignmentIndex);
foreach (var unalignedTime in unalignedTimes)
{
var alignedTime = alignmentIndex.Alignment.RegressionLine.GetY(unalignedTime);
times.Add(alignedTime);
}
}
}
return times.ToArray();
}
/// <summary>
/// Returns the times at which a peptide was found in a particular file.
/// </summary>
public double[] GetRetentionTimes(LibraryRetentionTimes retentionTimes, string sequence, ExplicitMods mods)
{
return (from typedSequence in GetTypedSequences(sequence, mods)
from time in retentionTimes.GetRetentionTimes(typedSequence.ModifiedSequence)
select time)
.ToArray();
}
public double[] GetAllRetentionTimes(string filePath, string peptideSequence, ExplicitMods explicitMods)
{
return GetAllRetentionTimes(MsDataFileUri.Parse(filePath), peptideSequence, explicitMods);
}
public void ResetMods()
{
// CONSIDER: This means once a peptide with variable modifications is explicitly
// modified, it is then treated the same as an unmodified peptide for
// future resets.
var explicitModsOrig = NodePeptide.ExplicitMods;
if (!NodePeptide.HasVariableMods)
ExplicitMods = null;
else if (!explicitModsOrig.HasHeavyModifications)
ExplicitMods = explicitModsOrig;
else
{
// Construct a new explicit mods with only the variable modifications
ExplicitMods = new ExplicitMods(NodePeptide.Peptide,
explicitModsOrig.StaticModifications,
new TypedExplicitModifications[0],
true);
}
var modifications = DocSettings.PeptideSettings.Modifications;
for (int i = 0; i < _listComboStatic.Count; i++)
{
UpdateComboItems(_listComboStatic[i],
StaticList,
ExplicitMods != null ? ExplicitMods.StaticModifications : null,
modifications.StaticModifications,
i,
ExplicitMods != null && ExplicitMods.IsVariableStaticMods,
true);
}
for (int i = 0; i < _listLabelTypeHeavy.Count; i++)
{
var labelType = _listLabelTypeHeavy[i];
var listComboHeavy = _listListComboHeavy[i];
for (int j = 0; j < listComboHeavy.Count; j++)
{
UpdateComboItems(listComboHeavy[j], HeavyList, null,
modifications.GetModifications(labelType), j, false, true);
}
}
}
public double[] GetUnalignedRetentionTimes(string peptideSequence, ExplicitMods explicitMods)
{
var times = new List<double>();
var modifiedSequences = GetTypedSequences(peptideSequence, explicitMods)
.Select(typedSequence => typedSequence.ModifiedSequence).ToArray();
foreach (var library in PeptideSettings.Libraries.Libraries)
{
if (null == library)
{
continue;
}
foreach (var source in library.ListRetentionTimeSources())
{
int? index = null;
times.AddRange(library.GetRetentionTimesWithSequences(source.Name, modifiedSequences, ref index));
}
}
return times.ToArray();
}
