private const string LAB_AUTHORITY = "proteome.gs.washington.edu"; // Not L10N
public ImportPeptideSearch()
{
SearchFilenames = new string[0];
CutoffScore = Settings.Default.LibraryResultCutOff;
SpectrumSourceFiles = new Dictionary <string, FoundResultsFilePossibilities>();
_matcher = new LibKeyModificationMatcher();
UserDefinedTypedMods = new HashSet <StaticMod>();
}
public ImportPeptideSearch()
{
SearchFilenames = new string[0];
CutoffScore = Settings.Default.LibraryResultCutOff;
SpectrumSourceFiles = new Dictionary<string, FoundResultsFilePossibilities>();
_matcher = new LibKeyModificationMatcher();
UserDefinedTypedMods = new HashSet<StaticMod>();
}
public ViewLibraryPepMatching(SrmDocument document,
Library library,
LibrarySpec spec,
byte[] lookupPool,
LibKeyModificationMatcher matcher,
ViewLibraryPepInfo[] peptides)
{
_document = document;
_selectedLibrary = library;
_selectedSpec = spec;
_lookupPool = lookupPool;
_matcher = matcher;
_libraryPepInfos = peptides;
_chargeSettingsMap = new SrmSettings[128];
}
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));
}
}