/// <summary>
/// Writes a protein database in mzLibProteinDb format, with additional modifications from the AdditionalModsToAddToProteins list.
/// </summary>
/// <param name="additionalModsToAddToProteins"></param>
/// <param name="proteinList"></param>
/// <param name="outputFileName"></param>
/// <returns>The new "modified residue" entries that are added due to being in the Mods dictionary</returns>
public static Dictionary <string, int> WriteXmlDatabase(Dictionary <string, HashSet <Tuple <int, Modification> > > additionalModsToAddToProteins,
List <Protein> proteinList, string outputFileName)
{
additionalModsToAddToProteins = additionalModsToAddToProteins ?? new Dictionary <string, HashSet <Tuple <int, Modification> > >();
// write nonvariant proteins (for cases where variants aren't applied, this just gets the protein itself)
List <Protein> nonVariantProteins = proteinList.Select(p => p.NonVariantProtein).Distinct().ToList();
var xmlWriterSettings = new XmlWriterSettings
{
Indent = true,
IndentChars = " "
};
Dictionary <string, int> newModResEntries = new Dictionary <string, int>();
using (XmlWriter writer = XmlWriter.Create(outputFileName, xmlWriterSettings))
{
writer.WriteStartDocument();
writer.WriteStartElement("mzLibProteinDb");
List <Modification> myModificationList = new List <Modification>();
foreach (Protein p in nonVariantProteins)
{
foreach (KeyValuePair <int, List <Modification> > entry in p.OneBasedPossibleLocalizedModifications)
{
myModificationList.AddRange(entry.Value);
}
}
HashSet <Modification> allRelevantModifications = new HashSet <Modification>(
nonVariantProteins.SelectMany(p => p.SequenceVariations.SelectMany(sv => sv.OneBasedModifications).Concat(p.OneBasedPossibleLocalizedModifications).SelectMany(kv => kv.Value))
.Concat(additionalModsToAddToProteins.Where(kv => nonVariantProteins.SelectMany(p => p.SequenceVariations.Select(sv => VariantApplication.GetAccession(p, new[] { sv })).Concat(new[] { p.Accession })).Contains(kv.Key)).SelectMany(kv => kv.Value.Select(v => v.Item2))));
foreach (Modification mod in allRelevantModifications.OrderBy(m => m.IdWithMotif))
{
writer.WriteStartElement("modification");
writer.WriteString(mod.ToString() + Environment.NewLine + "//");
writer.WriteEndElement();
}
foreach (Protein protein in nonVariantProteins)
{
writer.WriteStartElement("entry");
writer.WriteStartElement("accession");
writer.WriteString(protein.Accession);
writer.WriteEndElement();
if (protein.Name != null)
{
writer.WriteStartElement("name");
writer.WriteString(protein.Name);
writer.WriteEndElement();
}
if (protein.FullName != null)
{
writer.WriteStartElement("protein");
writer.WriteStartElement("recommendedName");
writer.WriteStartElement("fullName");
writer.WriteString(protein.FullName);
writer.WriteEndElement();
writer.WriteEndElement();
writer.WriteEndElement();
}
writer.WriteStartElement("gene");
foreach (var gene_name in protein.GeneNames)
{
writer.WriteStartElement("name");
writer.WriteAttributeString("type", gene_name.Item1);
writer.WriteString(gene_name.Item2);
writer.WriteEndElement();
}
writer.WriteEndElement();
if (protein.Organism != null)
{
writer.WriteStartElement("organism");
writer.WriteStartElement("name");
writer.WriteAttributeString("type", "scientific");
writer.WriteString(protein.Organism);
writer.WriteEndElement();
writer.WriteEndElement();
}
foreach (var dbRef in protein.DatabaseReferences)
{
writer.WriteStartElement("dbReference");
writer.WriteAttributeString("type", dbRef.Type);
writer.WriteAttributeString("id", dbRef.Id);
foreach (Tuple <string, string> property in dbRef.Properties)
{
writer.WriteStartElement("property");
writer.WriteAttributeString("type", property.Item1);
writer.WriteAttributeString("value", property.Item2);
writer.WriteEndElement();
}
writer.WriteEndElement();
}
foreach (var proteolysisProduct in protein.ProteolysisProducts)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", proteolysisProduct.Type);
writer.WriteStartElement("location");
writer.WriteStartElement("begin");
writer.WriteAttributeString("position", proteolysisProduct.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
writer.WriteStartElement("end");
writer.WriteAttributeString("position", proteolysisProduct.OneBasedEndPosition.ToString());
writer.WriteEndElement();
writer.WriteEndElement();
writer.WriteEndElement();
}
foreach (var hm in GetModsForThisProtein(protein, null, additionalModsToAddToProteins, newModResEntries).OrderBy(b => b.Key))
{
foreach (var modId in hm.Value)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", "modified residue");
writer.WriteAttributeString("description", modId);
writer.WriteStartElement("location");
writer.WriteStartElement("position");
writer.WriteAttributeString("position", hm.Key.ToString(CultureInfo.InvariantCulture));
writer.WriteEndElement();
writer.WriteEndElement();
writer.WriteEndElement();
}
}
foreach (var hm in protein.SequenceVariations)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", "sequence variant");
writer.WriteAttributeString("description", hm.Description.ToString());
writer.WriteStartElement("original");
writer.WriteString(hm.OriginalSequence);
writer.WriteEndElement(); // original
writer.WriteStartElement("variation");
writer.WriteString(hm.VariantSequence);
writer.WriteEndElement(); // variation
writer.WriteStartElement("location");
if (hm.OneBasedBeginPosition == hm.OneBasedEndPosition)
{
writer.WriteStartElement("position");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
}
else
{
writer.WriteStartElement("begin");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
writer.WriteStartElement("end");
writer.WriteAttributeString("position", hm.OneBasedEndPosition.ToString());
writer.WriteEndElement();
}
foreach (var hmm in GetModsForThisProtein(protein, hm, additionalModsToAddToProteins, newModResEntries).OrderBy(b => b.Key))
{
foreach (var modId in hmm.Value)
{
writer.WriteStartElement("subfeature");
writer.WriteAttributeString("type", "modified residue");
writer.WriteAttributeString("description", modId);
writer.WriteStartElement("location");
writer.WriteStartElement("subposition");
writer.WriteAttributeString("subposition", hmm.Key.ToString(CultureInfo.InvariantCulture));
writer.WriteEndElement();
writer.WriteEndElement();
writer.WriteEndElement();
}
}
writer.WriteEndElement(); // location
writer.WriteEndElement(); // feature
}
foreach (var hm in protein.DisulfideBonds)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", "disulfide bond");
writer.WriteAttributeString("description", hm.Description);
writer.WriteStartElement("location");
if (hm.OneBasedBeginPosition == hm.OneBasedEndPosition)
{
writer.WriteStartElement("position");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
}
else
{
writer.WriteStartElement("begin");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
writer.WriteStartElement("end");
writer.WriteAttributeString("position", hm.OneBasedEndPosition.ToString());
writer.WriteEndElement();
}
writer.WriteEndElement(); // location
writer.WriteEndElement(); // feature
}
foreach (var hm in protein.SpliceSites)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", "splice site");
writer.WriteAttributeString("description", hm.Description.ToString());
writer.WriteStartElement("location");
if (hm.OneBasedBeginPosition == hm.OneBasedEndPosition)
{
writer.WriteStartElement("position");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
}
else
{
writer.WriteStartElement("begin");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement();
writer.WriteStartElement("end");
writer.WriteAttributeString("position", hm.OneBasedEndPosition.ToString());
writer.WriteEndElement();
}
writer.WriteEndElement(); // location
writer.WriteEndElement(); // feature
}
foreach (var hm in protein.SpliceVariants)
{
writer.WriteStartElement("feature");
writer.WriteAttributeString("type", "splice variant"); //TODO should id be stored or not written?
writer.WriteAttributeString("description", hm.Description);
if (!hm.VariantSequence.Equals(""))
{
writer.WriteStartElement("original");
writer.WriteString(hm.OriginalSequence);
writer.WriteEndElement(); // original
writer.WriteStartElement("variation");
writer.WriteString(hm.VariantSequence);
writer.WriteEndElement(); // variation
}
writer.WriteStartElement("location");
if (hm.OneBasedBeginPosition == hm.OneBasedEndPosition)
{
writer.WriteStartElement("position");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement(); // position
}
else
{
writer.WriteStartElement("begin");
writer.WriteAttributeString("position", hm.OneBasedBeginPosition.ToString());
writer.WriteEndElement(); // begin
writer.WriteStartElement("end");
writer.WriteAttributeString("position", hm.OneBasedEndPosition.ToString());
writer.WriteEndElement(); // end
}
writer.WriteEndElement(); // location
writer.WriteEndElement(); // feature
}
writer.WriteStartElement("sequence");
writer.WriteAttributeString("length", protein.Length.ToString(CultureInfo.InvariantCulture));
writer.WriteString(protein.BaseSequence);
writer.WriteEndElement(); // sequence
writer.WriteEndElement(); // entry
}
writer.WriteEndElement(); // mzLibProteinDb
writer.WriteEndDocument();
}
return(newModResEntries);
}
private static Dictionary <int, HashSet <string> > GetModsForThisProtein(Protein protein, SequenceVariation seqvar, Dictionary <string, HashSet <Tuple <int, Modification> > > additionalModsToAddToProteins, Dictionary <string, int> newModResEntries)
{
var modsToWriteForThisSpecificProtein = new Dictionary <int, HashSet <string> >();
var primaryModDict = seqvar == null ? protein.OneBasedPossibleLocalizedModifications : seqvar.OneBasedModifications;
foreach (var mods in primaryModDict)
{
foreach (var mod in mods.Value)
{
if (modsToWriteForThisSpecificProtein.TryGetValue(mods.Key, out HashSet <string> val))
{
val.Add(mod.IdWithMotif);
}
else
{
modsToWriteForThisSpecificProtein.Add(mods.Key, new HashSet <string> {
mod.IdWithMotif
});
}
}
}
string accession = seqvar == null ? protein.Accession : VariantApplication.GetAccession(protein, new[] { seqvar });
if (additionalModsToAddToProteins.ContainsKey(accession))
{
foreach (var ye in additionalModsToAddToProteins[accession])
{
int additionalModResidueIndex = ye.Item1;
string additionalModId = ye.Item2.IdWithMotif;
bool modAdded = false;
// If we already have modifications that need to be written to the specific residue, get the hash set of those mods
if (modsToWriteForThisSpecificProtein.TryGetValue(additionalModResidueIndex, out HashSet <string> val))
{
// Try to add the new mod to that hash set. If it's not there, modAdded=true, and it is added.
modAdded = val.Add(additionalModId);
}
// Otherwise, no modifications currently need to be written to the residue at residueIndex, so need to create new hash set for that residue
else
{
modsToWriteForThisSpecificProtein.Add(additionalModResidueIndex, new HashSet <string> {
additionalModId
});
modAdded = true;
}
// Finally, if a new modification has in fact been deemed worthy of being added to the database, mark that in the output dictionary
if (modAdded)
{
if (newModResEntries.ContainsKey(additionalModId))
{
newModResEntries[additionalModId]++;
}
else
{
newModResEntries.Add(additionalModId, 1);
}
}
}
}
return(modsToWriteForThisSpecificProtein);
}
public static void TestSearchPtmVariantDatabase()
{
//Create Search Task
SearchTask task1 = new SearchTask
{
SearchParameters = new SearchParameters
{
SearchTarget = true,
MassDiffAcceptorType = MassDiffAcceptorType.Exact,
},
CommonParameters = new CommonParameters(digestionParams: new DigestionParams(minPeptideLength: 5))
};
//add task to task list
var taskList = new List <(string, MetaMorpheusTask)> {
("task1", task1)
};
//create modification lists
List <Modification> variableModifications = GlobalVariables.AllModsKnown.OfType <Modification>().Where
(b => task1.CommonParameters.ListOfModsVariable.Contains((b.ModificationType, b.IdWithMotif))).ToList();
//protein Creation (One with mod and one without)
ModificationMotif.TryGetMotif("P", out ModificationMotif motifP);
ModificationMotif.TryGetMotif("K", out ModificationMotif motifK);
var variant = new SequenceVariation(3, "P", "K", @"1\t50000000\t.\tA\tG\t.\tPASS\tANN=G|||||||||||||||||||\tGT:AD:DP\t1/1:30,30:30");
Protein testProteinWithMod = new Protein("PEPTID", "accession1", sequenceVariations: new List <SequenceVariation> {
variant
});
string variantAcc = VariantApplication.GetAccession(testProteinWithMod, new[] { variant });
//First Write XML Database
string xmlName = "oblm.xml";
//Add Mod to list and write XML input database
var modList = new Dictionary <string, HashSet <Tuple <int, Modification> > >();
var hash = new HashSet <Tuple <int, Modification> >
{
new Tuple <int, Modification>(1, new Modification(_originalId: "acetyl on P", _modificationType: "type", _target: motifP, _monoisotopicMass: 42, _locationRestriction: "Anywhere.")),
};
var hashVar = new HashSet <Tuple <int, Modification> >
{
new Tuple <int, Modification>(3, new Modification(_originalId: "acetyl on K", _modificationType: "type", _target: motifK, _monoisotopicMass: 42, _locationRestriction: "Anywhere.")),
};
modList.Add(testProteinWithMod.Accession, hash);
modList.Add(variantAcc, hashVar);
ProteinDbWriter.WriteXmlDatabase(modList, new List <Protein> {
testProteinWithMod
}, xmlName);
//now write MZML file
var variantProteins = ProteinDbLoader.LoadProteinXML(xmlName, true, DecoyType.Reverse, null, false, null, out var unknownModifications);
var variantProtein = variantProteins[0];
var variantDecoy = variantProteins[1];
Assert.AreEqual(0, unknownModifications.Count);
Assert.AreEqual(2, variantProteins.Count); // target & decoy
Assert.AreEqual(2, variantProteins[0].OneBasedPossibleLocalizedModifications.Count);
List <int> foundResidueIndicies = variantProtein.OneBasedPossibleLocalizedModifications.Select(k => k.Key).ToList();
List <int> expectedResidueIndices = new List <int>()
{
1, 3
};
Assert.That(foundResidueIndicies, Is.EquivalentTo(expectedResidueIndices));
Assert.AreEqual(2, variantDecoy.OneBasedPossibleLocalizedModifications.Count);
foundResidueIndicies = variantDecoy.OneBasedPossibleLocalizedModifications.Select(k => k.Key).ToList();
expectedResidueIndices = new List <int>()
{
4, 6
}; //originally modified residues are now at the end in the decoy
Assert.That(foundResidueIndicies, Is.EquivalentTo(expectedResidueIndices));
var thisOk = unknownModifications; //for debugging
var commonParamsAtThisPoint = task1.CommonParameters.DigestionParams; //for debugging
var digestedList = variantProteins[0].GetVariantProteins()[0].Digest(task1.CommonParameters.DigestionParams, new List <Modification>(), variableModifications).ToList();
Assert.AreEqual(4, digestedList.Count);
//Set Peptide with 1 mod at position 3
PeptideWithSetModifications pepWithSetMods1 = digestedList[1];
//Finally Write MZML file
Assert.AreEqual("PEK[type:acetyl on K]TID", pepWithSetMods1.FullSequence);//this might be base sequence
MsDataFile myMsDataFile = new TestDataFile(new List <PeptideWithSetModifications> {
pepWithSetMods1
});
string mzmlName = @"hello.mzML";
IO.MzML.MzmlMethods.CreateAndWriteMyMzmlWithCalibratedSpectra(myMsDataFile, mzmlName, false);
//run!
var engine = new EverythingRunnerEngine(taskList, new List <string> {
mzmlName
},
new List <DbForTask> {
new DbForTask(xmlName, false)
}, Environment.CurrentDirectory);
engine.Run();
}