public void AddModification(StaticMod mod, IsotopeLabelType labelType)
{
if (MatcherPepMods.GetModificationTypes().Contains(labelType))
{
var newMods = MatcherPepMods.GetModifications(labelType)
.Where(existingMod => !existingMod.Equivalent(mod)).ToList();
newMods.Add(mod);
MatcherPepMods = MatcherPepMods.ChangeModifications(labelType, newMods);
}
else if (labelType.IsLight)
{
MatcherPepMods =
new PeptideModifications(new List<StaticMod> { mod }, MatcherPepMods.GetHeavyModifications().ToArray());
}
else
{
var typedHeavyMods =
new List<TypedModifications>(MatcherPepMods.GetHeavyModifications())
{ new TypedModifications(labelType, new List<StaticMod> { mod }) };
MatcherPepMods = new PeptideModifications(MatcherPepMods.StaticModifications, typedHeavyMods);
}
MatchesUpdated = true;
}
public void UpdateMatches(PeptideModifications prevPepMods, PeptideModifications newPepMods)
{
var labelTypes = newPepMods.GetModificationTypes().ToList();
labelTypes.AddRange(prevPepMods.GetModificationTypes());
foreach (var labelType in labelTypes)
{
var newMods = newPepMods.GetModifications(labelType);
var prevMods = prevPepMods.GetModifications(labelType);
// Add new modifications.
foreach (var mod in newMods.Where(newMod => !prevMods.Contains(prevMod => prevMod.Equivalent(newMod))))
{
AddModification(mod, labelType);
}
// Remove old modifications
foreach (var mod in prevMods.Where(prevMod => !newMods.Contains(newMod => newMod.Equivalent(prevMod))))
{
RemoveModification(mod, labelType);
}
}
}
public void OkDialog()
{
var helper = new MessageBoxHelper(this);
var charge = 0;
if (textCharge.Visible && !helper.ValidateSignedNumberTextBox(textCharge, _minCharge, _maxCharge, out charge))
return;
if (RetentionTimeWindow.HasValue && !RetentionTime.HasValue)
{
helper.ShowTextBoxError(textRetentionTimeWindow,
Resources.Peptide_ExplicitRetentionTimeWindow_Explicit_retention_time_window_requires_an_explicit_retention_time_value_);
return;
}
Charge = charge; // Note: order matters here, this settor indirectly updates _formulaBox.MonoMass when formula is empty
if (string.IsNullOrEmpty(_formulaBox.Formula))
{
// Can the text fields be understood as mz?
if (!_formulaBox.ValidateAverageText(helper))
return;
if (!_formulaBox.ValidateMonoText(helper))
return;
}
var formula = _formulaBox.Formula;
var monoMass = _formulaBox.MonoMass ?? 0;
var averageMass = _formulaBox.AverageMass ?? 0;
if (monoMass < CustomIon.MIN_MASS || averageMass < CustomIon.MIN_MASS)
{
_formulaBox.ShowTextBoxErrorFormula(helper,
string.Format(Resources.EditCustomMoleculeDlg_OkDialog_Custom_molecules_must_have_a_mass_greater_than_or_equal_to__0__,
CustomIon.MIN_MASS));
return;
}
if (monoMass > CustomIon.MAX_MASS || averageMass > CustomIon.MAX_MASS)
{
_formulaBox.ShowTextBoxErrorFormula(helper,
string.Format(Resources.EditCustomMoleculeDlg_OkDialog_Custom_molecules_must_have_a_mass_less_than_or_equal_to__0__, CustomIon.MAX_MASS));
return;
}
if ((_transitionSettings != null) &&
(!_transitionSettings.IsMeasurablePrecursor(BioMassCalc.CalculateIonMz(monoMass, charge)) ||
!_transitionSettings.IsMeasurablePrecursor(BioMassCalc.CalculateIonMz(averageMass, charge))))
{
_formulaBox.ShowTextBoxErrorFormula(helper, Resources.SkylineWindow_AddMolecule_The_precursor_m_z_for_this_molecule_is_out_of_range_for_your_instrument_settings_);
return;
}
if (!string.IsNullOrEmpty(_formulaBox.Formula))
{
try
{
ResultCustomIon = new DocNodeCustomIon(formula, textName.Text);
}
catch (InvalidDataException x)
{
_formulaBox.ShowTextBoxErrorFormula(helper, x.Message);
return;
}
}
else
{
ResultCustomIon = new DocNodeCustomIon(monoMass, averageMass, textName.Text);
}
// Did user change the list of heavy labels?
if (_driverLabelType != null)
{
PeptideModifications modifications = new PeptideModifications(
_peptideSettings.Modifications.StaticModifications,
_peptideSettings.Modifications.MaxVariableMods,
_peptideSettings.Modifications.MaxNeutralLosses,
_driverLabelType.GetHeavyModifications(), // This is the only thing the user may have altered
_peptideSettings.Modifications.InternalStandardTypes);
var settings = _peptideSettings.ChangeModifications(modifications);
// Only update if anything changed
if (!Equals(settings, _peptideSettings))
{
SrmSettings newSettings = _parent.DocumentUI.Settings.ChangePeptideSettings(settings);
if (!_parent.ChangeSettings(newSettings, true))
{
return;
}
_peptideSettings = newSettings.PeptideSettings;
}
}
// See if this combination of charge and label would conflict with any existing transition groups
if (_existingIds != null && _existingIds.Any(t =>
{
var transitionGroup = t as TransitionGroup;
return transitionGroup != null && Equals(transitionGroup.LabelType, IsotopeLabelType) &&
Equals(transitionGroup.PrecursorCharge, Charge) && !ReferenceEquals(t, _initialId);
}))
{
helper.ShowTextBoxError(textName,
Resources.EditCustomMoleculeDlg_OkDialog_A_precursor_with_that_charge_and_label_type_already_exists_, textName.Text);
return;
}
// See if this would conflict with any existing transitions
if (_existingIds != null && (_existingIds.Any(t =>
{
var transition = t as Transition;
return transition != null && ((transition.Charge == Charge) && Equals(transition.CustomIon, ResultCustomIon)) && !ReferenceEquals(t, _initialId);
})))
{
helper.ShowTextBoxError(textName,
Resources.EditCustomMoleculeDlg_OkDialog_A_similar_transition_already_exists_, textName.Text);
return;
}
DialogResult = DialogResult.OK;
}
private bool ImportSearchInternal(CommandArgs commandArgs, ref SrmDocument doc)
{
var progressMonitor = new CommandProgressMonitor(_out, new ProgressStatus(String.Empty));
var import = new ImportPeptideSearch
{
SearchFilenames = commandArgs.SearchResultsFiles.ToArray(),
CutoffScore = commandArgs.CutoffScore.GetValueOrDefault()
};
// Build library
var builder = import.GetLibBuilder(doc, commandArgs.Saving ? commandArgs.SaveFile : commandArgs.SkylineFile, commandArgs.IncludeAmbiguousMatches);
ImportPeptideSearch.ClosePeptideSearchLibraryStreams(doc);
_out.WriteLine(Resources.CommandLine_ImportSearch_Creating_spectral_library_from_files_);
foreach (var file in commandArgs.SearchResultsFiles)
_out.WriteLine(Path.GetFileName(file));
if (!builder.BuildLibrary(progressMonitor))
return false;
if (!string.IsNullOrEmpty(builder.AmbiguousMatchesMessage))
_out.WriteLine(builder.AmbiguousMatchesMessage);
var docLibSpec = builder.LibrarySpec.ChangeDocumentLibrary(true);
_out.WriteLine(Resources.CommandLine_ImportSearch_Loading_library);
var libraryManager = new LibraryManager();
if (!import.LoadPeptideSearchLibrary(libraryManager, docLibSpec, progressMonitor))
return false;
doc = import.AddDocumentSpectralLibrary(doc, docLibSpec);
if (doc == null)
return false;
if (!import.VerifyRetentionTimes(import.GetFoundResultsFiles().Select(f => f.Path)))
{
_out.WriteLine(TextUtil.LineSeparate(
Resources.ImportPeptideSearchDlg_NextPage_The_document_specific_spectral_library_does_not_have_valid_retention_times_,
Resources.ImportPeptideSearchDlg_NextPage_Please_check_your_peptide_search_pipeline_or_contact_Skyline_support_to_ensure_retention_times_appear_in_your_spectral_libraries_));
return false;
}
// Look for results files to import
import.InitializeSpectrumSourceFiles(doc);
import.UpdateSpectrumSourceFilesFromDirs(import.GetDirsToSearch(Path.GetDirectoryName(commandArgs.SkylineFile)), false, null);
var missingResultsFiles = import.GetMissingResultsFiles().ToArray();
if (missingResultsFiles.Any())
{
foreach (var file in missingResultsFiles)
{
if (doc.Settings.HasResults && doc.Settings.MeasuredResults.FindMatchingMSDataFile(new MsDataFilePath(file)) != null)
continue;
_out.WriteLine(Resources.CommandLine_ImportSearch_Warning__Unable_to_locate_results_file___0__, Path.GetFileName(file));
}
}
// Add all modifications, if requested
if (commandArgs.AcceptAllModifications)
{
import.InitializeModifications(doc);
var foundMods = import.GetMatchedMods().Count();
var newModifications = new PeptideModifications(import.MatcherPepMods.StaticModifications,
new[] {new TypedModifications(IsotopeLabelType.heavy, import.MatcherHeavyMods)});
var newSettings = import.AddModifications(doc, newModifications);
if (!ReferenceEquals(doc.Settings, newSettings))
{
if (foundMods != 1)
_out.WriteLine(Resources.CommandLine_ImportSearch_Adding__0__modifications_, foundMods);
else
_out.WriteLine(Resources.CommandLine_ImportSearch_Adding_1_modification_);
doc = doc.ChangeSettings(newSettings);
doc.Settings.UpdateDefaultModifications(false);
}
}
// Import FASTA
if (commandArgs.ImportingFasta)
{
_out.WriteLine(Resources.CommandLine_ImportFasta_Importing_FASTA_file__0____, Path.GetFileName(commandArgs.FastaPath));
doc = ImportPeptideSearch.PrepareImportFasta(doc);
int emptyProteins;
try
{
IdentityPath firstAdded, nextAdd;
doc = ImportPeptideSearch.ImportFasta(doc, commandArgs.FastaPath, progressMonitor, null,
out firstAdded, out nextAdd, out emptyProteins);
}
catch (Exception x)
{
_out.WriteLine(Resources.CommandLine_Run_Error__Failed_importing_the_file__0____1_, commandArgs.FastaPath, x.Message);
_doc = doc;
return true; // So that document will be saved with the new library
}
if (emptyProteins > 0 && !commandArgs.KeepEmptyProteins)
{
doc = ImportPeptideSearch.RemoveEmptyProteins(doc);
}
}
// Import results
_doc = doc;
ImportFoundResultsFiles(commandArgs, import);
return true;
}
public LabelTypeComboDriver(ComboBox combo,
PeptideModifications modifications,
SettingsListBoxDriver<StaticMod> driverHeavyMod,
Label labelIS,
ComboBox comboIS,
CheckedListBox listBoxIS)
{
_driverHeavyMod = driverHeavyMod;
LabelIS = labelIS;
Combo = combo;
Combo.DisplayMember = Resources.LabelTypeComboDriver_LabelTypeComboDriver_LabelType;
ComboIS = comboIS;
ListBoxIS = listBoxIS;
LoadList(null, modifications.InternalStandardTypes,
modifications.GetHeavyModifications().ToArray());
ShowModifications();
}
public void TestModificationMatcher()
{
InitSeqs();
var carbC = StaticModList.GetDefaultsOn()[0];
// Test exception thrown if unable to match - mass.
UpdateMatcherFail(STR_FAIL_MASS);
UpdateMatcherFail(STR_FAIL_NOT_A_NUMBER);
// Test exception thrown if unable to match - name.
UpdateMatcherFail(STR_FAIL_NAME);
// Can't match empty modifications.
UpdateMatcherFail(STR_FAIL_EMPTY_MOD);
UpdateMatcherFail(STR_FAIL_EMPTY_MOD2);
// Can't match double modifications.
UpdateMatcherFail(STR_FAIL_DOUBLE_MOD);
// Test exception thrown if unimod not specified correctly
UpdateMatcherFail(STR_FAIL_UNIMOD);
UpdateMatcherFail(STR_UNKNOWN_UNIMOD);
// Can't phosphorylate tryptophan
UpdateMatcherFail(STR_FAIL_WRONG_AA_UNIMOD);
// Can't put C-terminal modification in middle of peptide
UpdateMatcherFail(STR_FAIL_UNIMOD_TERMINUS);
// Test mods in UniMod match correctly.
UpdateMatcher(StaticModList.GetDefaultsOn(), HeavyModList.GetDefaultsOn(), null, null);
// A sequence with no modifications should not be explicitly modified.
Assert.IsFalse(MATCHER.GetModifiedNode(STR_NO_MODS).HasExplicitMods);
var nodeCysOxi = MATCHER.GetModifiedNode(STR_CYS_AND_OXI);
Assert.IsTrue(nodeCysOxi.HasExplicitMods);
Assert.IsFalse(nodeCysOxi.ExplicitMods.HasHeavyModifications);
// Modifications should match by name.
Assert.IsTrue(MATCHER.GetModifiedNode(STR_MOD_BY_NAME).ExplicitMods.StaticModifications.Contains(mod =>
Equals(mod.Modification.Name, "Phospho (ST)")));
// Test can find terminal modification
Assert.IsTrue(MATCHER.GetModifiedNode(STR_TERM_ONLY).ExplicitMods.HeavyModifications.Contains(mod =>
mod.Modification.EquivalentAll(UniMod.GetModification("Label:13C(6) (C-term R)", false))));
// Test can find matches on terminus that are not terminal
Assert.IsTrue(MATCHER.GetModifiedNode(STR_MOD_BY_NAME).ExplicitMods.StaticModifications.Contains(mod =>
mod.Modification.Terminus == null));
// Test matching negative masses
Assert.IsTrue(MATCHER.GetModifiedNode(STR_AMMONIA_LOSS).ExplicitMods.StaticModifications.Contains(mod =>
mod.Modification.EquivalentAll(UniMod.GetModification("Ammonia-loss (N-term C)", true))));
// General and specific
// If all AAs modified, try for most general modification.
Assert.IsTrue(MATCHER.GetModifiedNode(STR_HEAVY_15)
.ExplicitMods.HeavyModifications.Contains(mod => mod.Modification.Equivalent(LABEL15_N)));
// Updating the settings.
// Peptide settings should change to include new mods.
var docNew = new SrmDocument(SrmSettingsList.GetDefault());
IdentityPath firstAdded;
IdentityPath nextAdded;
docNew = docNew.AddPeptideGroups(new[] { new PeptideGroupDocNode(new PeptideGroup(), "PepGroup1", "",
new[] {MATCHER.GetModifiedNode(STR_MOD_BY_NAME)})}, true, null, out firstAdded, out nextAdded);
var pepSetNew = MATCHER.GetDocModifications(docNew);
Assert.IsTrue(pepSetNew.StaticModifications.Contains(UniMod.GetModification("Phospho (ST)", true).ChangeExplicit(true)));
// Update the document to the new settings.
var pepSetNew1 = pepSetNew;
var settingsNew2 = docNew.Settings.ChangePeptideModifications(mods => pepSetNew1);
var lightGlobalMods = new MappedList<string, StaticMod>();
lightGlobalMods.AddRange(settingsNew2.PeptideSettings.Modifications.StaticModifications);
var heavyGlobalMods = new MappedList<string, StaticMod>();
heavyGlobalMods.AddRange(settingsNew2.PeptideSettings.Modifications.HeavyModifications);
// Match again. Test FoundMatches string should now be empty.
MATCHER.CreateMatches(docNew.Settings.ChangePeptideModifications(mods => pepSetNew1),
new List<string> { STR_MOD_BY_NAME }, lightGlobalMods, heavyGlobalMods);
Assert.IsTrue(string.IsNullOrEmpty(MATCHER.FoundMatches));
// Adding 15N to the settings.
UpdateMatcher(new[] { carbC }, new[] { LABEL15_N }, null, null);
// Test sequences with only explicit heavy mods should not have explicit light mods
Assert.IsNull(MATCHER.GetModifiedNode(STR_HEAVY_ONLY).ExplicitMods.StaticModifications);
// Test sequences with only explicit light mods should not have explicit heavy mods
Assert.IsFalse(MATCHER.GetModifiedNode(STR_LIGHT_ONLY).ExplicitMods.HasHeavyModifications);
// Test global mods take precendence over UniMod
UpdateMatcher(new[] { carbC }, null, new[] { OXIDATION_M_GLOBAL }, new[] { LABEL15_N });
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).ExplicitMods.StaticModifications
.Contains(mod => Equals(mod.Modification, OXIDATION_M_GLOBAL)));
// Test document mods take precendence over UniMod
UpdateMatcher(new[] { carbC, METHIONINE_OXIDATION }, null, new[] { OXIDATION_M_GLOBAL }, new[] { LABEL15_N });
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).HasExplicitMods);
// Test exception thrown if match doesn't make sense - wrong AA.
UpdateMatcherFail(STR_FAIL_OX_ON_D);
// Test exception thrown if match doesn't make sense - wrong terminus.
_seqs.Add(STR_FAIL_OX_TERM);
AssertEx.ThrowsException<FormatException>(() => UpdateMatcher(new[] {OXIDATION_M_C_TERM}, null, null, null));
_seqs.Remove(STR_FAIL_OX_TERM);
// Heavy 15N - All AAs.
UpdateMatcher(new[] { carbC, METHIONINE_OXIDATION }, new[] {LABEL15_N}, null, null);
// Node should be created from document settings if possible.
Assert.IsNull(MATCHER.GetModifiedNode(STR_HEAVY_15).ExplicitMods);
// Heavy 15N - specific AA.
// If only a specific AA is modified, there must be an explicit mod.
Assert.IsTrue(MATCHER.GetModifiedNode(STR_HEAVY_15_F).HasExplicitMods);
// Test variable mods match correctly.
// Put variable mod in global mod and not on doc - make sure don't get variable mod,
// should get explicit mod in that case.
var variableMetOx = METHIONINE_OXIDATION.ChangeVariable(true);
UpdateMatcher(new[] { carbC }, null, new[] { variableMetOx }, null);
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).HasExplicitMods);
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_OXI_PHOS).ExplicitMods.IsVariableStaticMods);
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_OXI_PHOS_CAP).ExplicitMods.IsVariableStaticMods);
// Add variable mod to doc
UpdateMatcher(new[] { carbC, variableMetOx }, null, null, null);
// Mod can be created by the settings.
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).HasExplicitMods);
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).ExplicitMods.IsVariableStaticMods);
// Mod cannot be created by the settings.
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_OXI_PHOS).ExplicitMods.IsVariableStaticMods);
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_OXI_PHOS_CAP).ExplicitMods.IsVariableStaticMods);
// Add Met Ox to global. Test: +16 finds it.
UpdateMatcher(new[] {carbC}, null, new[] {MET_OX_ROUNDED}, null);
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).
ExplicitMods.StaticModifications.Contains(mod => Equals(mod.Modification, MET_OX_ROUNDED)));
// Test: +15.99 finds UniMod.
Assert.IsFalse(MATCHER.GetModifiedNode(STR_HEAVY_15).
ExplicitMods.StaticModifications.Contains(mod => Equals(mod.Modification, MET_OX_ROUNDED)));
// Add Methionine Oxidation before Met Ox. Test: +16 finds it.
UpdateMatcher(new[] { carbC }, null, new[] { METHIONINE_OXIDATION, MET_OX_ROUNDED }, null);
Assert.IsFalse(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).
ExplicitMods.StaticModifications.Contains(mod => Equals(mod.Modification, MET_OX_ROUNDED)));
Assert.IsTrue(MATCHER.GetModifiedNode(STR_CYS_AND_OXI).
ExplicitMods.StaticModifications.Contains(mod => Equals(mod.Modification, METHIONINE_OXIDATION)));
// Test long masses rounded.
Assert.IsTrue(MATCHER.GetModifiedNode(STR_METOX_LONG_MASS).ExplicitMods.StaticModifications.Contains(mod =>
Equals(mod.Modification, METHIONINE_OXIDATION)));
// Test UniMod label types
var node = MATCHER.GetModifiedNode(STR_UNIMOD_LABEL);
Assert.IsNotNull(node);
Assert.IsNull(node.ExplicitMods.StaticModifications);
Assert.IsTrue(node.ExplicitMods.HeavyModifications.Contains(mod =>
Equals(mod.Modification, N_TERM_LABEL)));
UpdateMatcherWithNoSequences(new[] { carbC }, new[] { N_TERM_LABEL }, new[] { METHIONINE_OXIDATION, MET_OX_ROUNDED }, null);
var nodeNew = MATCHER.GetModifiedNode(STR_UNIMOD_LABEL);
Assert.IsNotNull(nodeNew);
Assert.IsTrue(nodeNew.TransitionGroups.Any(group => Equals(group.TransitionGroup.LabelType, IsotopeLabelType.heavy)));
UpdateMatcher(new[] { carbC }, null, new[] { METHIONINE_OXIDATION, MET_OX_ROUNDED }, null);
// Test case where there are lots of unimod labels
var nodeUniAll = MATCHER.GetModifiedNode(STR_UNIMOD_ALL);
Assert.AreEqual(nodeUniAll.ExplicitMods.HeavyModifications.Count, 10);
Assert.IsNull(nodeUniAll.ExplicitMods.StaticModifications);
foreach (var mod in nodeUniAll.ExplicitMods.HeavyModifications)
{
Assert.AreEqual(mod.Modification.ShortName, "+01");
Assert.AreEqual(mod.Modification.UnimodId, 994);
}
// Test unimod terminal label
var nodeUniTerm = MATCHER.GetModifiedNode(STR_UNIMOD_TERMINUS);
Assert.AreEqual(nodeUniTerm.ExplicitMods.HeavyModifications.Count, 1);
Assert.IsNull(nodeUniTerm.ExplicitMods.StaticModifications);
Assert.AreEqual(nodeUniTerm.ExplicitMods.HeavyModifications[0].Modification.Terminus, ModTerminus.C);
Assert.AreEqual(nodeUniTerm.ExplicitMods.HeavyModifications[0].Modification.UnimodId, 298);
// Basic multi-label test
var heavyLabelType2 = new IsotopeLabelType("Heavy2", 1);
var typedMod = new TypedModifications(heavyLabelType2, new List<StaticMod> { LABEL15_N });
var peptideMods = new PeptideModifications(new List<StaticMod>(), new List<TypedModifications> { typedMod });
var settingsMultiLabel = SrmSettingsList.GetDefault().ChangePeptideModifications(mods => peptideMods);
var defSetSetLight = new MappedList<string, StaticMod>();
defSetSetLight.AddRange(StaticModList.GetDefaultsOn());
var defSetHeavy = new MappedList<string, StaticMod>();
defSetHeavy.AddRange(HeavyModList.GetDefaultsOn());
defSetHeavy.Add( LABEL15_N );
MATCHER.CreateMatches(settingsMultiLabel, new List<string> { STR_HEAVY_15_F }, defSetSetLight, defSetHeavy);
Assert.IsTrue(MATCHER.GetModifiedNode(STR_HEAVY_15_F).ExplicitMods.GetHeavyModifications().Contains(mod => Equals(mod.LabelType, heavyLabelType2)));
// Peptide settings should not change.
var docNew0 = new SrmDocument(settingsMultiLabel).AddPeptideGroups(new[] { new PeptideGroupDocNode(new PeptideGroup(),
"PepGroup1", "", new[] {MATCHER.GetModifiedNode(STR_HEAVY_15_F)})}, true, null, out firstAdded, out nextAdded);
var settingsNew = MATCHER.GetDocModifications(docNew0);
Assert.AreEqual(settingsMultiLabel.PeptideSettings.Modifications, settingsNew);
// Finding specific modifications.
// If only specific AA modified, try for most specific modification.
UpdateMatcher(null, null, null, null, new[] { STR_HEAVY_15_F});
Assert.IsTrue(MATCHER.GetModifiedNode(STR_HEAVY_15_F)
.ExplicitMods.HeavyModifications.Contains(mod =>
mod.Modification.AminoAcids.Contains(c => c == 'F')));
// If only some AAs modified, try for most specific modifications.
UpdateMatcher(null, null, null, null, new[] { STR_HEAVY_15_NOT_ALL });
Assert.IsTrue(MATCHER.GetModifiedNode(STR_HEAVY_15_NOT_ALL)
.ExplicitMods.HeavyModifications.Contains(mod =>
mod.Modification.AminoAcids.Contains(c => c == 'I')));
using (var testDir = new TestFilesDir(TestContext, ZIP_FILE))
{
var modMatchDocContainer = InitMatchDocContainer(testDir);
var libkeyModMatcher = new LibKeyModificationMatcher();
var anlLibSpec = new BiblioSpecLiteSpec("ANL_Combo", testDir.GetTestPath("ANL_Combined.blib"));
var yeastLibSpec = new BiblioSpecLiteSpec("Yeast", testDir.GetTestPath("Yeast_atlas_small.blib"));
modMatchDocContainer.ChangeLibSpecs(new[] { anlLibSpec, yeastLibSpec });
var docLibraries = modMatchDocContainer.Document.Settings.PeptideSettings.Libraries.Libraries;
int anlLibIndex = docLibraries.IndexOf(library => Equals(library.Name, anlLibSpec.Name));
int yeastLibIndex = docLibraries.IndexOf(library => Equals(library.Name, yeastLibSpec.Name));
libkeyModMatcher.CreateMatches(modMatchDocContainer.Document.Settings,
docLibraries[anlLibIndex].Keys, defSetSetLight, defSetHeavy);
// Test can match 15N
Assert.IsTrue(libkeyModMatcher.Matches.Values.Contains(match =>
match.HeavyMod != null && match.HeavyMod.Equivalent(LABEL15_N)));
var uniModMetOx = UniMod.GetModification("Oxidation (M)", true);
// Test can match Met Ox
Assert.IsTrue(libkeyModMatcher.Matches.Values.Contains(match =>
match.StructuralMod != null && match.StructuralMod.Equivalent(uniModMetOx)));
// Test can match 15N and Met ox!
Assert.IsTrue(libkeyModMatcher.Matches.Contains(match => match.Key.Mass == 17
&& match.Value.StructuralMod != null && match.Value.StructuralMod.Equivalent(uniModMetOx)
&& match.Value.HeavyMod != null && match.Value.HeavyMod.Equivalent(LABEL15_N)));
// Test can match Cysteine (Implicit) and Met Ox (variable)
libkeyModMatcher.CreateMatches(modMatchDocContainer.Document.Settings,
docLibraries[yeastLibIndex].Keys, defSetSetLight, defSetHeavy);
Assert.IsTrue(libkeyModMatcher.MatcherPepMods.StaticModifications.Contains(mod =>
mod.Formula.Equals(UniMod.GetModification(StaticModList.DEFAULT_NAME, true).Formula) && !mod.IsVariable));
Assert.IsTrue(libkeyModMatcher.MatcherPepMods.StaticModifications.Contains(mod =>
mod.Formula.Equals("O") && mod.IsVariable));
}
}
public PeptideSettings ChangeModifications(PeptideModifications prop)
{
return ChangeProp(ImClone(this), im => im.Modifications = prop);
}
private PeptideSettings ValidateNewSettings(bool showMessages)
{
var helper = new MessageBoxHelper(this, showMessages);
// Validate and hold digestion settings
Enzyme enzyme = Settings.Default.GetEnzymeByName(comboEnzyme.SelectedItem.ToString());
Helpers.AssignIfEquals(ref enzyme, _peptideSettings.Enzyme);
int maxMissedCleavages =
int.Parse(comboMissedCleavages.SelectedItem.ToString());
bool excludeRaggedEnds = cbRaggedEnds.Checked;
DigestSettings digest = new DigestSettings(maxMissedCleavages, excludeRaggedEnds);
Helpers.AssignIfEquals(ref digest, Digest);
var backgroundProteomeSpec = _driverBackgroundProteome.SelectedItem;
BackgroundProteome backgroundProteome = BackgroundProteome.NONE;
if (!backgroundProteomeSpec.IsNone)
{
backgroundProteome = new BackgroundProteome(backgroundProteomeSpec, true);
if (backgroundProteome.DatabaseInvalid)
{
var message = TextUtil.LineSeparate(string.Format(Resources.PeptideSettingsUI_ValidateNewSettings_Failed_to_load_background_proteome__0__,
backgroundProteomeSpec.Name),
string.Format(Resources.PeptideSettingsUI_ValidateNewSettings_The_file__0__may_not_be_a_valid_proteome_file,
backgroundProteomeSpec.DatabasePath));
MessageDlg.Show(this, message);
tabControl1.SelectedIndex = 0;
_driverBackgroundProteome.Combo.Focus();
return null;
}
}
Helpers.AssignIfEquals(ref backgroundProteome, _peptideSettings.BackgroundProteome);
// Validate and hold prediction settings
string nameRT = comboRetentionTime.SelectedItem.ToString();
RetentionTimeRegression retentionTime =
Settings.Default.GetRetentionTimeByName(nameRT);
if (retentionTime != null && retentionTime.Calculator != null)
{
RetentionScoreCalculatorSpec retentionCalc =
Settings.Default.GetCalculatorByName(retentionTime.Calculator.Name);
// Just in case the calculator in use in the current documet got removed,
// never set the calculator to null. Just keep using the one we have.
if (retentionCalc != null && !ReferenceEquals(retentionCalc, retentionTime.Calculator))
retentionTime = retentionTime.ChangeCalculator(retentionCalc);
}
bool useMeasuredRT = cbUseMeasuredRT.Checked;
double? measuredRTWindow = null;
if (!string.IsNullOrEmpty(textMeasureRTWindow.Text))
{
double measuredRTWindowOut;
const double minWindow = PeptidePrediction.MIN_MEASURED_RT_WINDOW;
const double maxWindow = PeptidePrediction.MAX_MEASURED_RT_WINDOW;
if (!helper.ValidateDecimalTextBox(tabControl1, (int) TABS.Prediction,
textMeasureRTWindow, minWindow, maxWindow, out measuredRTWindowOut))
return null;
measuredRTWindow = measuredRTWindowOut;
}
string nameDt = comboDriftTimePredictor.SelectedItem.ToString();
DriftTimePredictor driftTimePredictor =
Settings.Default.GetDriftTimePredictorByName(nameDt);
if (driftTimePredictor != null && driftTimePredictor.IonMobilityLibrary != null)
{
IonMobilityLibrarySpec ionMobilityLibrary =
Settings.Default.GetIonMobilityLibraryByName(driftTimePredictor.IonMobilityLibrary.Name);
// Just in case the library in use in the current documet got removed,
// never set the library to null. Just keep using the one we have.
if (ionMobilityLibrary != null && !ReferenceEquals(ionMobilityLibrary, driftTimePredictor.IonMobilityLibrary))
driftTimePredictor = driftTimePredictor.ChangeLibrary(ionMobilityLibrary);
}
bool useLibraryDriftTime = cbUseSpectralLibraryDriftTimes.Checked;
double? libraryDTResolvingPower = null;
if (useLibraryDriftTime || !string.IsNullOrEmpty(textSpectralLibraryDriftTimesResolvingPower.Text))
{
double libraryDTWindowOut;
if (!helper.ValidateDecimalTextBox(tabControl1, (int)TABS.Prediction,
textSpectralLibraryDriftTimesResolvingPower, null, null, out libraryDTWindowOut))
return null;
string errmsg = EditDriftTimePredictorDlg.ValidateResolvingPower(libraryDTWindowOut);
if (errmsg != null)
{
helper.ShowTextBoxError(tabControl1, (int)TABS.Prediction, textSpectralLibraryDriftTimesResolvingPower, errmsg);
return null;
}
libraryDTResolvingPower = libraryDTWindowOut;
}
var prediction = new PeptidePrediction(retentionTime, driftTimePredictor, useMeasuredRT, measuredRTWindow, useLibraryDriftTime, libraryDTResolvingPower);
Helpers.AssignIfEquals(ref prediction, Prediction);
// Validate and hold filter settings
int excludeNTermAAs;
if (!helper.ValidateNumberTextBox(tabControl1, (int) TABS.Filter, textExcludeAAs,
PeptideFilter.MIN_EXCLUDE_NTERM_AA, PeptideFilter.MAX_EXCLUDE_NTERM_AA, out excludeNTermAAs))
return null;
int minPeptideLength;
if (!helper.ValidateNumberTextBox(tabControl1, (int) TABS.Filter, textMinLength,
PeptideFilter.MIN_MIN_LENGTH, PeptideFilter.MAX_MIN_LENGTH, out minPeptideLength))
return null;
int maxPeptideLength;
if (!helper.ValidateNumberTextBox(tabControl1, (int)TABS.Filter, textMaxLength,
Math.Max(PeptideFilter.MIN_MAX_LENGTH, minPeptideLength), PeptideFilter.MAX_MAX_LENGTH, out maxPeptideLength))
return null;
PeptideExcludeRegex[] exclusions = _driverExclusion.Chosen;
bool autoSelect = cbAutoSelect.Checked;
PeptideFilter filter;
try
{
filter = new PeptideFilter(excludeNTermAAs,
minPeptideLength,
maxPeptideLength,
exclusions,
autoSelect);
}
catch (InvalidDataException x)
{
if (showMessages)
MessageDlg.ShowException(this, x);
return null;
}
Helpers.AssignIfEquals(ref filter, Filter);
// Validate and hold libraries
PeptideLibraries libraries;
IList<LibrarySpec> librarySpecs = _driverLibrary.Chosen;
if (librarySpecs.Count == 0)
libraries = new PeptideLibraries(PeptidePick.library, null, null, false, librarySpecs, new Library[0]);
else
{
int? peptideCount = null;
if (cbLimitPeptides.Checked)
{
int peptideCountVal;
if (!helper.ValidateNumberTextBox(textPeptideCount, PeptideLibraries.MIN_PEPTIDE_COUNT,
PeptideLibraries.MAX_PEPTIDE_COUNT, out peptideCountVal))
return null;
peptideCount = peptideCountVal;
}
PeptidePick pick = (PeptidePick) comboMatching.SelectedIndex;
IList<Library> librariesLoaded = new Library[librarySpecs.Count];
bool documentLibrary = false;
if (Libraries != null)
{
// Use existing library spec's, if nothing was changed.
// Avoid changing the libraries, just because the the picking
// algorithm changed.
if (ArrayUtil.EqualsDeep(librarySpecs, Libraries.LibrarySpecs))
{
librarySpecs = Libraries.LibrarySpecs;
librariesLoaded = Libraries.Libraries;
}
documentLibrary = Libraries.HasDocumentLibrary;
// Otherwise, leave the list of loaded libraries empty,
// and let the LibraryManager refill it. This ensures a
// clean save of library specs only in the user config, rather
// than a mix of library specs and libraries.
}
PeptideRankId rankId = (PeptideRankId) comboRank.SelectedItem;
if (comboRank.SelectedIndex == 0)
rankId = null;
libraries = new PeptideLibraries(pick, rankId, peptideCount, documentLibrary, librarySpecs, librariesLoaded);
}
Helpers.AssignIfEquals(ref libraries, Libraries);
// Validate and hold modifications
int maxVariableMods;
if (!helper.ValidateNumberTextBox(tabControl1, (int)TABS.Modifications, textMaxVariableMods,
PeptideModifications.MIN_MAX_VARIABLE_MODS, PeptideModifications.MAX_MAX_VARIABLE_MODS, out maxVariableMods))
return null;
int maxNeutralLosses;
if (!helper.ValidateNumberTextBox(tabControl1, (int)TABS.Modifications, textMaxNeutralLosses,
PeptideModifications.MIN_MAX_NEUTRAL_LOSSES, PeptideModifications.MAX_MAX_NEUTRAL_LOSSES, out maxNeutralLosses))
return null;
var standardTypes = _driverLabelType.InternalStandardTypes;
PeptideModifications modifications = new PeptideModifications(
_driverStaticMod.Chosen, maxVariableMods, maxNeutralLosses,
_driverLabelType.GetHeavyModifications(), standardTypes);
// Should not be possible to change explicit modifications in the background,
// so this should be safe. CONSIDER: Document structure because of a library load?
modifications = modifications.DeclareExplicitMods(_parent.DocumentUI,
Settings.Default.StaticModList, Settings.Default.HeavyModList);
Helpers.AssignIfEquals(ref modifications, _peptideSettings.Modifications);
PeptideIntegration integration = new PeptideIntegration(_driverPeakScoringModel.SelectedItem);
Helpers.AssignIfEquals(ref integration, Integration);
QuantificationSettings quantification = QuantificationSettings.DEFAULT
.ChangeNormalizationMethod(comboNormalizationMethod.SelectedItem as NormalizationMethod ?? NormalizationMethod.NONE)
.ChangeRegressionWeighting(comboWeighting.SelectedItem as RegressionWeighting)
.ChangeRegressionFit(comboRegressionFit.SelectedItem as RegressionFit)
.ChangeMsLevel(_quantMsLevels[comboQuantMsLevel.SelectedIndex])
.ChangeUnits(tbxQuantUnits.Text);
return new PeptideSettings(enzyme, digest, prediction, filter, libraries, modifications, integration, backgroundProteome)
.ChangeAbsoluteQuantification(quantification);
}
public PeptideSettings(Enzyme enzyme,
DigestSettings digestSettings,
PeptidePrediction prediction,
PeptideFilter filter,
PeptideLibraries libraries,
PeptideModifications modifications,
PeptideIntegration integration,
BackgroundProteome backgroundProteome
)
{
Enzyme = enzyme;
DigestSettings = digestSettings;
Prediction = prediction;
Filter = filter;
Libraries = libraries;
Modifications = modifications;
Integration = integration;
BackgroundProteome = backgroundProteome;
Quantification = QuantificationSettings.DEFAULT;
}
public bool Equals(PeptideModifications obj)
{
if (ReferenceEquals(null, obj)) return false;
if (ReferenceEquals(this, obj)) return true;
return obj.MaxVariableMods == MaxVariableMods &&
obj.MaxNeutralLosses == MaxNeutralLosses &&
ArrayUtil.EqualsDeep(obj.InternalStandardTypes, InternalStandardTypes) &&
ArrayUtil.EqualsDeep(obj._modifications, _modifications);
}
public static void SetSerializationContext(PeptideModifications mods)
{
_serializationContext = mods;
}
public PeptideDocNode EnsureMods(PeptideModifications source, PeptideModifications target,
MappedList<string, StaticMod> defSetStat, MappedList<string, StaticMod> defSetHeavy)
{
// Create explicit mods matching the implicit mods on this peptide for each document.
var sourceImplicitMods = new ExplicitMods(this, source.StaticModifications, defSetStat, source.GetHeavyModifications(), defSetHeavy);
var targetImplicitMods = new ExplicitMods(this, target.StaticModifications, defSetStat, target.GetHeavyModifications(), defSetHeavy);
// If modifications match, no need to create explicit modifications for the peptide.
if (sourceImplicitMods.Equals(targetImplicitMods))
return this;
// Add explicit mods if static mods not implicit in the target document.
IList<ExplicitMod> newExplicitStaticMods = null;
bool preserveVariable = HasVariableMods;
// Preserve non-variable explicit modifications
if (!preserveVariable && HasExplicitMods && ExplicitMods.StaticModifications != null)
{
// If they are not the same as the implicit modifications in the new document
if (!ArrayUtil.EqualsDeep(ExplicitMods.StaticModifications, targetImplicitMods.StaticModifications))
newExplicitStaticMods = ExplicitMods.StaticModifications;
}
else if (!ArrayUtil.EqualsDeep(sourceImplicitMods.StaticModifications, targetImplicitMods.StaticModifications))
{
preserveVariable = false;
newExplicitStaticMods = sourceImplicitMods.StaticModifications;
}
else if (preserveVariable)
{
newExplicitStaticMods = ExplicitMods.StaticModifications;
}
// Drop explicit mods if matching implicit mods are found in the target document.
IList<TypedExplicitModifications> newExplicitHeavyMods = new List<TypedExplicitModifications>();
// For each heavy label type, add explicit mods if static mods not found in the target document.
var newTypedStaticMods = newExplicitStaticMods != null
? new TypedExplicitModifications(Peptide, IsotopeLabelType.light, newExplicitStaticMods)
: null;
foreach (TypedExplicitModifications targetDocMod in targetImplicitMods.GetHeavyModifications())
{
// Use explicit modifications when available. Otherwise, compare against new implicit modifications
IList<ExplicitMod> heavyMods = (HasExplicitMods ? ExplicitMods.GetModifications(targetDocMod.LabelType) : null) ??
sourceImplicitMods.GetModifications(targetDocMod.LabelType);
if (heavyMods != null && !ArrayUtil.EqualsDeep(heavyMods, targetDocMod.Modifications) && heavyMods.Count > 0)
{
var newTypedHeavyMods = new TypedExplicitModifications(Peptide, targetDocMod.LabelType, heavyMods);
newTypedHeavyMods = newTypedHeavyMods.AddModMasses(newTypedStaticMods);
newExplicitHeavyMods.Add(newTypedHeavyMods);
}
}
if (newExplicitStaticMods != null || newExplicitHeavyMods.Count > 0)
return ChangeExplicitMods(new ExplicitMods(Peptide, newExplicitStaticMods, newExplicitHeavyMods, preserveVariable));
return ChangeExplicitMods(null);
}
public SrmSettings AddModifications(SrmDocument document, PeptideModifications modifications)
{
_matcher.MatcherPepMods = modifications;
return document.Settings.ChangePeptideModifications(mods => _matcher.SafeMergeImplicitMods(document));
}
