public NeutralTerminusFragment(FragmentationTerminus terminus, double neutralMass, int fragmentNumber, int aminoAcidPosition)
{
this.Terminus = terminus;
this.NeutralMass = (double)ClassExtensions.RoundedDouble(neutralMass);
this.FragmentNumber = fragmentNumber;
this.AminoAcidPosition = aminoAcidPosition;
}
public static List <Modification> GetVariableTerminalMods(FragmentationTerminus fragmentationTerminus, List <Modification> variableModifications)
{
string terminalStringToFind = fragmentationTerminus == FragmentationTerminus.N ? "C-terminal" : "N-terminal"; //if singleN, want to find c-terminal mods and vice-versa
return(variableModifications == null ?
new List <Modification>() :
variableModifications.Where(x => x.LocationRestriction.Contains(terminalStringToFind)).ToList());
}
private static List <MatchedFragmentIon> ReadFragmentIonsFromString(string matchedMzString, string peptideBaseSequence)
{
var peaks = matchedMzString.Split(MzSplit, StringSplitOptions.RemoveEmptyEntries).Select(v => v.Trim())
.ToList();
peaks.RemoveAll(p => p.Contains("\""));
List <MatchedFragmentIon> matchedIons = new List <MatchedFragmentIon>();
foreach (var peak in peaks)
{
var split = peak.Split(new char[] { '+', ':' });
string ionTypeAndNumber = split[0];
Match result = IonParser.Match(ionTypeAndNumber);
ProductType productType = (ProductType)Enum.Parse(typeof(ProductType), result.Groups[1].Value);
int fragmentNumber = int.Parse(result.Groups[2].Value);
int z = int.Parse(split[1]);
double mz = double.Parse(split[2], CultureInfo.InvariantCulture);
double neutralLoss = 0;
// check for neutral loss
if (ionTypeAndNumber.Contains("-"))
{
string temp = ionTypeAndNumber.Replace("(", "");
temp = temp.Replace(")", "");
var split2 = temp.Split('-');
neutralLoss = double.Parse(split2[1], CultureInfo.InvariantCulture);
}
FragmentationTerminus terminus = FragmentationTerminus.None;
if (TerminusSpecificProductTypes.ProductTypeToFragmentationTerminus.ContainsKey(productType))
{
terminus = TerminusSpecificProductTypes.ProductTypeToFragmentationTerminus[productType];
}
int aminoAcidPosition = fragmentNumber;
if (terminus == FragmentationTerminus.C)
{
aminoAcidPosition = peptideBaseSequence.Length - fragmentNumber;
}
Product p = new Product(productType,
terminus,
mz.ToMass(z) - DissociationTypeCollection.GetMassShiftFromProductType(productType),
fragmentNumber,
aminoAcidPosition,
neutralLoss);
matchedIons.Add(new MatchedFragmentIon(ref p, mz, 1.0, z));
}
return(matchedIons);
}
/// <summary>
/// A product is the individual neutral fragment from an MS dissociation. A fragmentation product here contains one of the two termini (N- or C-).
/// The ProductType describes where along the backbone the fragmentaiton occurred (e.g. b-, y-, c-, zdot-). The neutral loss mass (if any) that
/// occurred from a mod on the fragment is listed as a mass. Finally the neutral mass of the whole fragment is provided.
/// </summary>
public Product(ProductType productType, FragmentationTerminus terminus, double neutralMass,
int fragmentNumber, int aminoAcidPosition, double neutralLoss)
{
NeutralMass = neutralMass;
ProductType = productType;
NeutralLoss = neutralLoss;
Terminus = terminus;
FragmentNumber = fragmentNumber;
AminoAcidPosition = aminoAcidPosition;
}
public readonly int SecondaryFragmentNumber; //used for internal fragment ions
/// <summary>
/// A product is the individual neutral fragment from an MS dissociation. A fragmentation product here contains one of the two termini (N- or C-).
/// The ProductType describes where along the backbone the fragmentaiton occurred (e.g. b-, y-, c-, zdot-). The neutral loss mass (if any) that
/// occurred from a mod on the fragment is listed as a mass. Finally the neutral mass of the whole fragment is provided.
/// </summary>
public Product(ProductType productType, FragmentationTerminus terminus, double neutralMass,
int fragmentNumber, int aminoAcidPosition, double neutralLoss, ProductType?secondaryProductType = null, int secondaryFragmentNumber = 0)
{
NeutralMass = neutralMass;
ProductType = productType;
NeutralLoss = neutralLoss;
Terminus = terminus;
FragmentNumber = fragmentNumber;
AminoAcidPosition = aminoAcidPosition;
SecondaryProductType = secondaryProductType;
SecondaryFragmentNumber = secondaryFragmentNumber;
}
public DigestionParams(string protease = "trypsin", int maxMissedCleavages = 2, int minPeptideLength = 7, int maxPeptideLength = int.MaxValue,
int maxModificationIsoforms = 1024, InitiatorMethionineBehavior initiatorMethionineBehavior = InitiatorMethionineBehavior.Variable,
int maxModsForPeptides = 2, bool semiProteaseDigestion = false, FragmentationTerminus terminusTypeSemiProtease = FragmentationTerminus.N)
{
Protease = ProteaseDictionary.Dictionary[protease];
MaxMissedCleavages = maxMissedCleavages;
MinPeptideLength = minPeptideLength;
MaxPeptideLength = maxPeptideLength;
MaxModificationIsoforms = maxModificationIsoforms;
InitiatorMethionineBehavior = initiatorMethionineBehavior;
MaxModsForPeptide = maxModsForPeptides;
SemiProteaseDigestion = semiProteaseDigestion;
TerminusTypeSemiProtease = terminusTypeSemiProtease;
}
/// <summary>
/// Generates theoretical fragments for given dissociation type for this peptide
/// </summary>
public IEnumerable <Product> Fragment(DissociationType dissociationType, FragmentationTerminus fragmentationTerminus)
{
// molecular ion
//yield return new Product(ProductType.M, new NeutralTerminusFragment(FragmentationTerminus.None, this.MonoisotopicMass, Length, Length), 0);
var productCollection = TerminusSpecificProductTypes.ProductIonTypesFromSpecifiedTerminus[fragmentationTerminus].Intersect(DissociationTypeCollection.ProductsFromDissociationType[dissociationType]);
List <(ProductType, int)> skippers = new List <(ProductType, int)>();
foreach (var product in productCollection.Where(f => f != ProductType.zPlusOne))
{
skippers.Add((product, BaseSequence.Length));
}
switch (dissociationType)
{
case DissociationType.CID:
skippers.Add((ProductType.b, 1));
break;
case DissociationType.ETD:
case DissociationType.ECD:
case DissociationType.EThcD:
skippers.AddRange(GetProlineZIonIndicies());
break;
}
foreach (var productType in productCollection)
{
// we're separating the N and C terminal masses and computing a separate compact peptide for each one
// this speeds calculations up without producing unnecessary terminus fragment info
FragmentationTerminus temporaryFragmentationTerminus = TerminusSpecificProductTypes.ProductTypeToFragmentationTerminus[productType];
NeutralTerminusFragment[] terminalMasses = CompactPeptide(temporaryFragmentationTerminus).TerminalMasses;
for (int f = 0; f < terminalMasses.Length; f++)
{
// fragments with neutral loss
if (AllModsOneIsNterminus.TryGetValue(terminalMasses[f].AminoAcidPosition + 1, out Modification mod) && mod.NeutralLosses != null &&
mod.NeutralLosses.TryGetValue(dissociationType, out List <double> neutralLosses))
{
foreach (double neutralLoss in neutralLosses)
{
if (neutralLoss == 0)
{
continue;
}
for (int n = f; n < terminalMasses.Length; n++)
{
if (!skippers.Contains((productType, terminalMasses[n].FragmentNumber)))
} //used to look for unlabeled proteins (in addition to labeled proteins) for SILAC experiments
public override bool Equals(object obj)
{
return(obj is DigestionParams a &&
MaxMissedCleavages.Equals(a.MaxMissedCleavages) &&
MinPeptideLength.Equals(a.MinPeptideLength) &&
MaxPeptideLength.Equals(a.MaxPeptideLength) &&
InitiatorMethionineBehavior.Equals(a.InitiatorMethionineBehavior) &&
MaxModificationIsoforms.Equals(a.MaxModificationIsoforms) &&
MaxModsForPeptide.Equals(a.MaxModsForPeptide) &&
Protease.Equals(a.Protease) &&
SearchModeType.Equals(a.SearchModeType) &&
FragmentationTerminus.Equals(a.FragmentationTerminus) &&
GeneratehUnlabeledProteinsForSilac.Equals(a.GeneratehUnlabeledProteinsForSilac));
}
public DigestionParams(string protease = "trypsin", int maxMissedCleavages = 2, int minPeptideLength = 7, int maxPeptideLength = int.MaxValue,
int maxModificationIsoforms = 1024, InitiatorMethionineBehavior initiatorMethionineBehavior = InitiatorMethionineBehavior.Variable,
int maxModsForPeptides = 2, CleavageSpecificity searchModeType = CleavageSpecificity.Full, FragmentationTerminus fragmentationTerminus = FragmentationTerminus.Both,
bool generateUnlabeledProteinsForSilac = true)
{
Protease = ProteaseDictionary.Dictionary[protease];
MaxMissedCleavages = maxMissedCleavages;
MinPeptideLength = minPeptideLength;
MaxPeptideLength = maxPeptideLength;
MaxModificationIsoforms = maxModificationIsoforms;
InitiatorMethionineBehavior = initiatorMethionineBehavior;
MaxModsForPeptide = maxModsForPeptides;
SearchModeType = searchModeType;
FragmentationTerminus = fragmentationTerminus;
RecordSpecificProtease();
GeneratehUnlabeledProteinsForSilac = generateUnlabeledProteinsForSilac;
}
private static List <MatchedFragmentIon> ReadFragmentIonsFromString(string matchedMzString, string matchedIntensityString, string peptideBaseSequence)
{
List <MatchedFragmentIon> matchedIons = new List <MatchedFragmentIon>();
if (matchedMzString.Length > 2) //check if there's an ion
{
List <string> peakMzs = CleanMatchedIonString(matchedMzString);
List <string> peakIntensities = CleanMatchedIonString(matchedIntensityString);
for (int index = 0; index < peakMzs.Count; index++)
{
string peak = peakMzs[index];
string[] split = peak.Split(new char[] { '+', ':' }); //TODO: needs update for negative charges that doesn't break internal fragment ions or neutral losses
double intensity = peakMzs.Count == peakIntensities.Count ? //TODO: needs update for negative charges that doesn't break internal fragment ions or neutral losses
double.Parse(peakIntensities[index].Split(new char[] { '+', ':', ']' })[2], CultureInfo.InvariantCulture) :
1.0;
int fragmentNumber = 0;
int secondaryFragmentNumber = 0;
ProductType productType;
ProductType? secondaryProductType = null;
FragmentationTerminus terminus = FragmentationTerminus.None; //default for internal fragments
int aminoAcidPosition;
double neutralLoss = 0;
//get theoretical fragment
string ionTypeAndNumber = split[0];
//if an internal fragment
if (ionTypeAndNumber.Contains("["))
{
string[] internalSplit = split[0].Split('[');
string[] productSplit = internalSplit[0].Split("I");
string[] positionSplit = internalSplit[1].Replace("]", "").Split('-');
productType = (ProductType)Enum.Parse(typeof(ProductType), productSplit[0]);
secondaryProductType = (ProductType)Enum.Parse(typeof(ProductType), productSplit[1]);
fragmentNumber = int.Parse(positionSplit[0]);
secondaryFragmentNumber = int.Parse(positionSplit[1]);
aminoAcidPosition = secondaryFragmentNumber - fragmentNumber;
}
else //terminal fragment
{
Match result = IonParser.Match(ionTypeAndNumber);
productType = (ProductType)Enum.Parse(typeof(ProductType), result.Groups[1].Value);
fragmentNumber = int.Parse(result.Groups[2].Value);
// check for neutral loss
if (ionTypeAndNumber.Contains("("))
{
string temp = ionTypeAndNumber.Replace("(", "");
temp = temp.Replace(")", "");
var split2 = temp.Split('-');
neutralLoss = double.Parse(split2[1], CultureInfo.InvariantCulture);
}
//get terminus
if (TerminusSpecificProductTypes.ProductTypeToFragmentationTerminus.ContainsKey(productType))
{
terminus = TerminusSpecificProductTypes.ProductTypeToFragmentationTerminus[productType];
}
//get amino acid position
aminoAcidPosition = terminus == FragmentationTerminus.C ?
peptideBaseSequence.Length - fragmentNumber :
fragmentNumber;
}
//get charge and mz
int z = int.Parse(split[1]);
double mz = double.Parse(split[2], CultureInfo.InvariantCulture);
Product p = new Product(productType,
terminus,
mz.ToMass(z),
fragmentNumber,
aminoAcidPosition,
neutralLoss,
secondaryProductType,
secondaryFragmentNumber);
matchedIons.Add(new MatchedFragmentIon(ref p, mz, intensity, z));
}
}
return(matchedIons);
}
private Tuple <int, PeptideWithSetModifications> Accepts(List <Product> fragments, double scanPrecursorMass, PeptideWithSetModifications peptide, FragmentationTerminus fragmentationTerminus, MassDiffAcceptor searchMode, bool semiSpecificSearch)
{
int localminPeptideLength = CommonParameters.DigestionParams.MinPeptideLength;
//Get terminal modifications, if any
Dictionary <int, List <Modification> > databaseAnnotatedMods = semiSpecificSearch ? null : GetTerminalModPositions(peptide, CommonParameters.DigestionParams, VariableTerminalModifications);
for (int i = localminPeptideLength - 1; i < fragments.Count; i++) //minus one start, because fragment 1 is at index 0
{
Product fragment = fragments[i];
double theoMass = fragment.NeutralMass - DissociationTypeCollection.GetMassShiftFromProductType(fragment.ProductType) + WaterMonoisotopicMass;
int notch = searchMode.Accepts(scanPrecursorMass, theoMass);
//check for terminal mods that might reach the observed mass
Modification terminalMod = null;
if (!semiSpecificSearch && notch < 0 && databaseAnnotatedMods.TryGetValue(i + 1, out List <Modification> terminalModsAtThisIndex)) //look for i+1, because the mod might exist at the terminus
{
foreach (Modification mod in terminalModsAtThisIndex)
{
notch = searchMode.Accepts(scanPrecursorMass, theoMass + mod.MonoisotopicMass.Value); //overwrite the notch, since the other notch wasn't accepted
if (notch >= 0)
{
terminalMod = mod;
break;
}
}
}
if (notch >= 0)
{
PeptideWithSetModifications updatedPwsm = null;
if (fragmentationTerminus == FragmentationTerminus.N)
{
int endResidue = peptide.OneBasedStartResidueInProtein + fragment.TerminusFragment.FragmentNumber - 1; //-1 for one based index
Dictionary <int, Modification> updatedMods = new Dictionary <int, Modification>();
foreach (KeyValuePair <int, Modification> mod in peptide.AllModsOneIsNterminus)
{
if (mod.Key < endResidue - peptide.OneBasedStartResidueInProtein + 3) //check if we cleaved it off, +1 for N-terminus being mod 1 and first residue being mod 2, +1 again for the -1 on end residue for one based index, +1 (again) for the one-based start residue
{
updatedMods.Add(mod.Key, mod.Value);
}
}
if (terminalMod != null)
{
updatedMods.Add(endResidue, terminalMod);
}
updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, peptide.OneBasedStartResidueInProtein, endResidue, CleavageSpecificity.Unknown, "", 0, updatedMods, 0);
}
else //if C terminal ions, shave off the n-terminus
{
int startResidue = peptide.OneBasedEndResidueInProtein - fragment.TerminusFragment.FragmentNumber + 1; //plus one for one based index
Dictionary <int, Modification> updatedMods = new Dictionary <int, Modification>(); //updateMods
int indexShift = startResidue - peptide.OneBasedStartResidueInProtein;
foreach (KeyValuePair <int, Modification> mod in peptide.AllModsOneIsNterminus)
{
if (mod.Key > indexShift + 1) //check if we cleaved it off, +1 for N-terminus being mod 1 and first residue being 2
{
int key = mod.Key - indexShift;
updatedMods.Add(key, mod.Value);
}
}
if (terminalMod != null)
{
updatedMods.Add(startResidue - 1, terminalMod);
}
updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, startResidue, peptide.OneBasedEndResidueInProtein, CleavageSpecificity.Unknown, "", 0, updatedMods, 0);
}
return(new Tuple <int, PeptideWithSetModifications>(notch, updatedPwsm));
}
else if (theoMass > scanPrecursorMass)
{
break;
}
}
//if the theoretical and experimental have the same mass or a terminal mod exists
if (peptide.BaseSequence.Length >= localminPeptideLength)
{
double totalMass = peptide.MonoisotopicMass;// + Constants.ProtonMass;
int notch = searchMode.Accepts(scanPrecursorMass, totalMass);
if (notch >= 0)
{
//need to update so that the cleavage specificity is recorded
PeptideWithSetModifications updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, peptide.OneBasedStartResidueInProtein, peptide.OneBasedEndResidueInProtein, CleavageSpecificity.Unknown, "", 0, peptide.AllModsOneIsNterminus, peptide.NumFixedMods);
return(new Tuple <int, PeptideWithSetModifications>(notch, updatedPwsm));
}
else //try a terminal mod (if it exists)
{
if (!semiSpecificSearch && databaseAnnotatedMods.TryGetValue(peptide.Length, out List <Modification> terminalModsAtThisIndex))
{
foreach (Modification terminalMod in terminalModsAtThisIndex)
{
notch = searchMode.Accepts(scanPrecursorMass, totalMass + terminalMod.MonoisotopicMass.Value); //overwrite the notch, since the other notch wasn't accepted
if (notch >= 0)
{
//need to update the mod dictionary and don't want to overwrite the peptide incase it's in other scans
Dictionary <int, Modification> updatedMods = new Dictionary <int, Modification>(); //updateMods
foreach (KeyValuePair <int, Modification> mod in peptide.AllModsOneIsNterminus)
{
updatedMods.Add(mod.Key, mod.Value);
}
//add the terminal mod
if (fragmentationTerminus == FragmentationTerminus.N)
{
updatedMods[peptide.OneBasedEndResidueInProtein] = terminalMod;
}
else
{
updatedMods[peptide.OneBasedStartResidueInProtein - 1] = terminalMod;
}
PeptideWithSetModifications updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, peptide.OneBasedStartResidueInProtein, peptide.OneBasedEndResidueInProtein, CleavageSpecificity.Unknown, "", 0, updatedMods, peptide.NumFixedMods);
return(new Tuple <int, PeptideWithSetModifications>(notch, updatedPwsm));
}
}
}
}
}
return(new Tuple <int, PeptideWithSetModifications>(-1, null));
}
/// <summary>
/// Generates theoretical fragments for given dissociation type for this peptide.
/// The "products" parameter is filled with these fragments.
/// </summary>
public void Fragment(DissociationType dissociationType, FragmentationTerminus fragmentationTerminus, List <Product> products)
{
// This code is specifically written to be memory- and CPU -efficient because it is
// called millions of times for a typical search (i.e., at least once per peptide).
// If you modify this code, BE VERY CAREFUL about allocating new memory, especially
// for new collections. This code also deliberately avoids using "yield return", again
// for performance reasons. Be sure to benchmark any changes with a parallelized
// fragmentation of every peptide in a database (i.e., test for speed decreases and
// memory issues).
products.Clear();
var massCaps = DissociationTypeCollection.GetNAndCTerminalMassShiftsForDissociationType(dissociationType);
double cTermMass = 0;
double nTermMass = 0;
List <ProductType> nTermProductTypes = DissociationTypeCollection.GetTerminusSpecificProductTypesFromDissociation(dissociationType, FragmentationTerminus.N);
List <ProductType> cTermProductTypes = DissociationTypeCollection.GetTerminusSpecificProductTypesFromDissociation(dissociationType, FragmentationTerminus.C);
bool calculateNTermFragments = fragmentationTerminus == FragmentationTerminus.N ||
fragmentationTerminus == FragmentationTerminus.Both;
bool calculateCTermFragments = fragmentationTerminus == FragmentationTerminus.C ||
fragmentationTerminus == FragmentationTerminus.Both;
//From http://www.matrixscience.com/help/fragmentation_help.html
//Low Energy CID -- In low energy CID(i.e.collision induced dissociation in a triple quadrupole or an ion trap) a peptide carrying a positive charge fragments mainly along its backbone,
//generating predominantly b and y ions. In addition, for fragments containing RKNQ, peaks are seen for ions that have lost ammonia (-17 Da) denoted a*, b* and y*. For fragments containing
//STED, loss of water(-18 Da) is denoted a°, b° and y°. Satellite ions from side chain cleavage are not observed.
bool haveSeenNTermDegreeIon = false;
bool haveSeenNTermStarIon = false;
bool haveSeenCTermDegreeIon = false;
bool haveSeenCTermStarIon = false;
// these two collections keep track of the neutral losses observed so far on the n-term or c-term.
// they are apparently necessary, but allocating memory for collections in this function results in
// inefficient memory usage and thus frequent garbage collection.
// TODO: If you can think of a way to remove these collections and still maintain correct
// fragmentation, please do so.
HashSet <double> nTermNeutralLosses = null;
HashSet <double> cTermNeutralLosses = null;
// n-terminus mod
if (calculateNTermFragments)
{
if (AllModsOneIsNterminus.TryGetValue(1, out Modification mod))
{
nTermMass += mod.MonoisotopicMass.Value;
}
}
// c-terminus mod
if (calculateCTermFragments)
{
if (AllModsOneIsNterminus.TryGetValue(BaseSequence.Length + 2, out Modification mod))
{
cTermMass += mod.MonoisotopicMass.Value;
}
}
for (int r = 0; r < BaseSequence.Length - 1; r++)
{
// n-term fragments
if (calculateNTermFragments)
{
char nTermResidue = BaseSequence[r];
// get n-term residue mass
if (Residue.TryGetResidue(nTermResidue, out Residue residue))
{
nTermMass += residue.MonoisotopicMass;
}
else
{
nTermMass = double.NaN;
}
// add side-chain mod
if (AllModsOneIsNterminus.TryGetValue(r + 2, out Modification mod))
{
nTermMass += mod.MonoisotopicMass.Value;
}
// handle star and degree ions for low-res CID
if (dissociationType == DissociationType.LowCID)
{
if (nTermResidue == 'R' || nTermResidue == 'K' || nTermResidue == 'N' || nTermResidue == 'Q')
{
haveSeenNTermStarIon = true;
}
if (nTermResidue == 'S' || nTermResidue == 'T' || nTermResidue == 'E' || nTermResidue == 'D')
{
haveSeenNTermDegreeIon = true;
}
}
// skip first N-terminal fragment (b1, aDegree1, ...) for CID
if (r == 0 && (dissociationType == DissociationType.CID || dissociationType == DissociationType.LowCID))
{
goto CTerminusFragments;
}
// generate products
for (int i = 0; i < nTermProductTypes.Count; i++)
{
if (dissociationType == DissociationType.LowCID)
{
if (!haveSeenNTermStarIon && (nTermProductTypes[i] == ProductType.aStar || nTermProductTypes[i] == ProductType.bStar))
{
continue;
}
if (!haveSeenNTermDegreeIon && (nTermProductTypes[i] == ProductType.aDegree || nTermProductTypes[i] == ProductType.bDegree))
{
continue;
}
}
products.Add(new Product(
nTermProductTypes[i],
FragmentationTerminus.N,
nTermMass + massCaps.Item1[i],
r + 1,
r + 1,
0));
if (mod != null && mod.NeutralLosses != null &&
mod.NeutralLosses.TryGetValue(dissociationType, out List <double> neutralLosses))
{
foreach (double neutralLoss in neutralLosses.Where(p => p != 0))
{
if (nTermNeutralLosses == null)
{
nTermNeutralLosses = new HashSet <double>();
}
nTermNeutralLosses.Add(neutralLoss);
}
}
if (nTermNeutralLosses != null)
{
foreach (double neutralLoss in nTermNeutralLosses)
{
products.Add(new Product(
nTermProductTypes[i],
FragmentationTerminus.N,
nTermMass + massCaps.Item1[i] - neutralLoss,
r + 1,
r + 1,
neutralLoss));
}
}
}
}
// c-term fragments
CTerminusFragments:
if (calculateCTermFragments)
{
char cTermResidue = BaseSequence[BaseSequence.Length - r - 1];
// get c-term residue mass
if (Residue.TryGetResidue(cTermResidue, out Residue residue))
{
cTermMass += residue.MonoisotopicMass;
}
else
{
cTermMass = double.NaN;
}
// add side-chain mod
if (AllModsOneIsNterminus.TryGetValue(BaseSequence.Length - r + 1, out Modification mod))
{
cTermMass += mod.MonoisotopicMass.Value;
}
// handle star and degree ions for low-res CID
if (dissociationType == DissociationType.LowCID)
{
if (cTermResidue == 'R' || cTermResidue == 'K' || cTermResidue == 'N' || cTermResidue == 'Q')
{
haveSeenCTermStarIon = true;
}
if (cTermResidue == 'S' || cTermResidue == 'T' || cTermResidue == 'E' || cTermResidue == 'D')
{
haveSeenCTermDegreeIon = true;
}
}
// generate products
for (int i = 0; i < cTermProductTypes.Count; i++)
{
// skip zDot ions for proline residues for ETD/ECD/EThcD
if (cTermResidue == 'P' &&
(dissociationType == DissociationType.ECD || dissociationType == DissociationType.ETD || dissociationType == DissociationType.EThcD) &&
cTermProductTypes[i] == ProductType.zDot)
{
continue;
}
if (dissociationType == DissociationType.LowCID)
{
if (!haveSeenCTermStarIon && cTermProductTypes[i] == ProductType.yStar)
{
continue;
}
if (!haveSeenCTermDegreeIon && cTermProductTypes[i] == ProductType.yDegree)
{
continue;
}
}
products.Add(new Product(
cTermProductTypes[i],
FragmentationTerminus.C,
cTermMass + massCaps.Item2[i],
r + 1,
BaseSequence.Length - r,
0));
if (mod != null && mod.NeutralLosses != null &&
mod.NeutralLosses.TryGetValue(dissociationType, out List <double> neutralLosses))
{
foreach (double neutralLoss in neutralLosses.Where(p => p != 0))
{
if (cTermNeutralLosses == null)
{
cTermNeutralLosses = new HashSet <double>();
}
cTermNeutralLosses.Add(neutralLoss);
}
}
if (cTermNeutralLosses != null)
{
foreach (double neutralLoss in cTermNeutralLosses)
{
products.Add(new Product(
cTermProductTypes[i],
FragmentationTerminus.C,
cTermMass + massCaps.Item2[i] - neutralLoss,
r + 1,
BaseSequence.Length - r,
neutralLoss));
}
}
}
}
}
// zDot generates one more ion...
if (cTermProductTypes.Contains(ProductType.zDot) && BaseSequence[0] != 'P')
{
// get c-term residue mass
if (Residue.TryGetResidue(BaseSequence[0], out Residue residue))
{
cTermMass += residue.MonoisotopicMass;
}
else
{
cTermMass = double.NaN;
}
// add side-chain mod
if (AllModsOneIsNterminus.TryGetValue(1, out Modification mod))
{
cTermMass += mod.MonoisotopicMass.Value;
}
// generate zDot product
products.Add(new Product(
ProductType.zDot,
FragmentationTerminus.C,
cTermMass + DissociationTypeCollection.GetMassShiftFromProductType(ProductType.zDot),
BaseSequence.Length,
1,
0));
if (mod != null && mod.NeutralLosses != null &&
mod.NeutralLosses.TryGetValue(dissociationType, out List <double> neutralLosses))
{
foreach (double neutralLoss in neutralLosses.Where(p => p != 0))
{
products.Add(new Product(
ProductType.zDot,
FragmentationTerminus.C,
cTermMass + DissociationTypeCollection.GetMassShiftFromProductType(ProductType.zDot) - neutralLoss,
BaseSequence.Length,
1,
neutralLoss));
}
}
}
foreach (var mod in AllModsOneIsNterminus.Where(p => p.Value.NeutralLosses != null))
{
// molecular ion minus neutral losses
if (mod.Value.NeutralLosses.TryGetValue(dissociationType, out List <double> losses))
{
foreach (double neutralLoss in losses.Where(p => p != 0))
{
if (neutralLoss != 0)
{
products.Add(new Product(ProductType.M, FragmentationTerminus.Both, MonoisotopicMass - neutralLoss, 0, 0, neutralLoss));
}
}
}
}
// generate diagnostic ions
// TODO: this code is memory-efficient but sort of CPU inefficient; it can be further optimized.
// however, diagnostic ions are fairly rare so it's probably OK for now
foreach (double diagnosticIon in AllModsOneIsNterminus.Where(p => p.Value.DiagnosticIons != null &&
p.Value.DiagnosticIons.ContainsKey(dissociationType)).SelectMany(p => p.Value.DiagnosticIons[dissociationType]).Distinct())
{
int diagnosticIonLabel = (int)Math.Round(diagnosticIon.ToMz(1), 0);
// the diagnostic ion is assumed to be annotated in the mod info as the *neutral mass* of the diagnostic ion, not the ionized species
products.Add(new Product(ProductType.D, FragmentationTerminus.Both, diagnosticIon, diagnosticIonLabel, 0, 0));
}
}
protected static IEnumerable <NeutralTerminusFragment> ComputeNeutralTerminusFragments(PeptideWithSetModifications peptide, FragmentationTerminus fragmentationTerminus)
{
double mass = 0;
if (fragmentationTerminus == FragmentationTerminus.N || fragmentationTerminus == FragmentationTerminus.Both)
{
for (int r = 0; r <= peptide.Length - 1; r++) //This is a zero based indexed for residues. The index of the first amino acid in the peptide is 0.
{
mass += Residue.ResidueMonoisotopicMass[peptide[r]]; //This is a zero based indexed for residues. The index of the first amino acid in the peptide is 0.
// side-chain mod
if (peptide.AllModsOneIsNterminus.TryGetValue(r + 2, out Modification currentModification))//This is a one based index. The index of the fragment from the first amino acid is 1.
{
mass += (double)currentModification.MonoisotopicMass;
}
// N-terminal mod
if (r == 0 && peptide.AllModsOneIsNterminus.TryGetValue(1, out currentModification))
{
mass += (double)currentModification.MonoisotopicMass;
}
if (r != peptide.Length - 1)
{
yield return(new NeutralTerminusFragment(FragmentationTerminus.N, mass, r + 1, r + 1));//This is a one based index. The index of the fragment from the first amino acid is 1.
}
}
}
if (fragmentationTerminus == FragmentationTerminus.C || fragmentationTerminus == FragmentationTerminus.Both)
{
mass = 0;
for (int r = peptide.Length - 1; r >= 0; r--)
{
mass += Residue.ResidueMonoisotopicMass[peptide[r]];
// side-chain mod
if (peptide.AllModsOneIsNterminus.TryGetValue(r + 2, out Modification currentModification))
{
mass += (double)currentModification.MonoisotopicMass;
}
// C-terminal mod
if (r == peptide.Length - 1 && peptide.AllModsOneIsNterminus.TryGetValue(peptide.Length + 2, out currentModification))
{
mass += (double)currentModification.MonoisotopicMass;
}
if (r != -1)
{
yield return(new NeutralTerminusFragment(FragmentationTerminus.C, mass, peptide.Length - r, r + 1));
}
}
}
}
private void SaveButton_Click(object sender, RoutedEventArgs e)
{
CleavageSpecificity searchModeType = CleavageSpecificity.Full; //classic and modern by default
if (semiSpecificSearchRadioButton.IsChecked.Value) //semi
{
searchModeType = CleavageSpecificity.Semi;
}
else if (nonSpecificSearchRadioButton.IsChecked.Value) //non
{
searchModeType = CleavageSpecificity.None;
}
//else it's the default of full
if (searchModeType != CleavageSpecificity.Full)
{
if (((Protease)proteaseComboBox.SelectedItem).Name.Contains("non-specific"))
{
searchModeType = CleavageSpecificity.None; //prevents an accidental semi attempt of a non-specific protease
if (cTerminalIons.IsChecked.Value)
{
Protease singleC = ProteaseDictionary.Dictionary["singleC"];
proteaseComboBox.SelectedItem = singleC;
}
else //we're not allowing no ion types. It must have N if it doesn't have C.
{
Protease singleN = ProteaseDictionary.Dictionary["singleN"];
proteaseComboBox.SelectedItem = singleN;
}
}
if (!addCompIonCheckBox.IsChecked.Value)
{
MessageBox.Show("Warning: Complementary ions are strongly recommended when using this algorithm.");
}
//only use N or C termini, not both
if (cTerminalIons.IsChecked.Value)
{
nTerminalIons.IsChecked = false;
}
else
{
nTerminalIons.IsChecked = true;
}
}
if (!GlobalGuiSettings.CheckTaskSettingsValidity(precursorMassToleranceTextBox.Text, productMassToleranceTextBox.Text, missedCleavagesTextBox.Text,
maxModificationIsoformsTextBox.Text, MinPeptideLengthTextBox.Text, MaxPeptideLengthTextBox.Text, maxThreadsTextBox.Text, minScoreAllowed.Text,
peakFindingToleranceTextBox.Text, histogramBinWidthTextBox.Text, DeconvolutionMaxAssumedChargeStateTextBox.Text, NumberOfPeaksToKeepPerWindowTextBox.Text,
MinimumAllowedIntensityRatioToBasePeakTexBox.Text, WindowWidthThomsonsTextBox.Text, NumberOfWindowsTextBox.Text, numberOfDatabaseSearchesTextBox.Text, MaxModNumTextBox.Text, MaxFragmentMassTextBox.Text, QValueTextBox.Text))
{
return;
}
Protease protease = (Protease)proteaseComboBox.SelectedItem;
DissociationType dissociationType = GlobalVariables.AllSupportedDissociationTypes[dissociationTypeComboBox.SelectedItem.ToString()];
CustomFragmentationWindow.Close();
FragmentationTerminus fragmentationTerminus = FragmentationTerminus.Both;
if (nTerminalIons.IsChecked.Value && !cTerminalIons.IsChecked.Value)
{
fragmentationTerminus = FragmentationTerminus.N;
}
else if (!nTerminalIons.IsChecked.Value && cTerminalIons.IsChecked.Value)
{
fragmentationTerminus = FragmentationTerminus.C;
}
else if (!nTerminalIons.IsChecked.Value && !cTerminalIons.IsChecked.Value) //why would you want this
{
fragmentationTerminus = FragmentationTerminus.None;
MessageBox.Show("Warning: No ion types were selected. MetaMorpheus will be unable to search MS/MS spectra.");
}
//else both
int maxMissedCleavages = string.IsNullOrEmpty(missedCleavagesTextBox.Text) ? int.MaxValue : (int.Parse(missedCleavagesTextBox.Text, NumberStyles.Any, CultureInfo.InvariantCulture));
int minPeptideLengthValue = (int.Parse(MinPeptideLengthTextBox.Text, NumberStyles.Any, CultureInfo.InvariantCulture));
int maxPeptideLengthValue = string.IsNullOrEmpty(MaxPeptideLengthTextBox.Text) ? int.MaxValue : (int.Parse(MaxPeptideLengthTextBox.Text, NumberStyles.Any, CultureInfo.InvariantCulture));
int MinVariantDepth = int.Parse(MinVariantDepthTextBox.Text, NumberStyles.Any, CultureInfo.InvariantCulture);
int MaxHeterozygousVariants = int.Parse(MaxHeterozygousVariantsTextBox.Text, NumberStyles.Any, CultureInfo.InvariantCulture);
int maxModificationIsoformsValue = (int.Parse(maxModificationIsoformsTextBox.Text, CultureInfo.InvariantCulture));
int maxModsForPeptideValue = (int.Parse(MaxModNumTextBox.Text, CultureInfo.InvariantCulture));
InitiatorMethionineBehavior initiatorMethionineBehavior = ((InitiatorMethionineBehavior)initiatorMethionineBehaviorComboBox.SelectedIndex);
DigestionParams digestionParamsToSave = new DigestionParams(
protease: protease.Name,
maxMissedCleavages: maxMissedCleavages,
minPeptideLength: minPeptideLengthValue,
maxPeptideLength: maxPeptideLengthValue,
maxModificationIsoforms: maxModificationIsoformsValue,
initiatorMethionineBehavior: initiatorMethionineBehavior,
maxModsForPeptides: maxModsForPeptideValue,
searchModeType: searchModeType,
fragmentationTerminus: fragmentationTerminus,
generateUnlabeledProteinsForSilac: CheckBoxQuantifyUnlabeledForSilac.IsChecked.Value);
Tolerance ProductMassTolerance;
if (productMassToleranceComboBox.SelectedIndex == 0)
{
ProductMassTolerance = new AbsoluteTolerance(double.Parse(productMassToleranceTextBox.Text, CultureInfo.InvariantCulture));
}
else
{
ProductMassTolerance = new PpmTolerance(double.Parse(productMassToleranceTextBox.Text, CultureInfo.InvariantCulture));
}
Tolerance PrecursorMassTolerance;
if (precursorMassToleranceComboBox.SelectedIndex == 0)
{
PrecursorMassTolerance = new AbsoluteTolerance(double.Parse(precursorMassToleranceTextBox.Text, CultureInfo.InvariantCulture));
}
else
{
PrecursorMassTolerance = new PpmTolerance(double.Parse(precursorMassToleranceTextBox.Text, CultureInfo.InvariantCulture));
}
TheTask.SearchParameters.MaxFragmentSize = Double.Parse(MaxFragmentMassTextBox.Text, CultureInfo.InvariantCulture);
var listOfModsVariable = new List <(string, string)>();
foreach (var heh in VariableModTypeForTreeViewObservableCollection)
{
listOfModsVariable.AddRange(heh.Children.Where(b => b.Use).Select(b => (b.Parent.DisplayName, b.ModName)));
}
var listOfModsFixed = new List <(string, string)>();
foreach (var heh in FixedModTypeForTreeViewObservableCollection)
{
listOfModsFixed.AddRange(heh.Children.Where(b => b.Use).Select(b => (b.Parent.DisplayName, b.ModName)));
}
if (!GlobalGuiSettings.VariableModCheck(listOfModsVariable))
{
return;
}
bool TrimMs1Peaks = trimMs1.IsChecked.Value;
bool TrimMsMsPeaks = trimMsMs.IsChecked.Value;
int?numPeaksToKeep = null;
if (int.TryParse(NumberOfPeaksToKeepPerWindowTextBox.Text, out int numberOfPeaksToKeeep))
{
numPeaksToKeep = numberOfPeaksToKeeep;
}
double?minimumAllowedIntensityRatioToBasePeak = null;
if (double.TryParse(MinimumAllowedIntensityRatioToBasePeakTexBox.Text, out double minimumAllowedIntensityRatio))
{
minimumAllowedIntensityRatioToBasePeak = minimumAllowedIntensityRatio;
}
double?windowWidthThompsons = null;
if (double.TryParse(WindowWidthThomsonsTextBox.Text, out double windowWidth))
{
windowWidthThompsons = windowWidth;
}
int?numberOfWindows = null;
if (int.TryParse(NumberOfWindowsTextBox.Text, out int numWindows))
{
numberOfWindows = numWindows;
}
bool normalizePeaksAccrossAllWindows = normalizePeaksInWindowCheckBox.IsChecked.Value;
bool parseMaxThreadsPerFile = !maxThreadsTextBox.Text.Equals("") && (int.Parse(maxThreadsTextBox.Text) <= Environment.ProcessorCount && int.Parse(maxThreadsTextBox.Text) > 0);
CommonParameters commonParamsToSave = new CommonParameters(
taskDescriptor: OutputFileNameTextBox.Text != "" ? OutputFileNameTextBox.Text : "SearchTask",
maxThreadsToUsePerFile: parseMaxThreadsPerFile ? int.Parse(maxThreadsTextBox.Text, CultureInfo.InvariantCulture) : new CommonParameters().MaxThreadsToUsePerFile,
useDeltaScore: deltaScoreCheckBox.IsChecked.Value,
reportAllAmbiguity: allAmbiguity.IsChecked.Value,
deconvolutionMaxAssumedChargeState: int.Parse(DeconvolutionMaxAssumedChargeStateTextBox.Text, CultureInfo.InvariantCulture),
totalPartitions: int.Parse(numberOfDatabaseSearchesTextBox.Text, CultureInfo.InvariantCulture),
doPrecursorDeconvolution: deconvolutePrecursors.IsChecked.Value,
useProvidedPrecursorInfo: useProvidedPrecursor.IsChecked.Value,
scoreCutoff: double.Parse(minScoreAllowed.Text, CultureInfo.InvariantCulture),
listOfModsFixed: listOfModsFixed,
listOfModsVariable: listOfModsVariable,
dissociationType: dissociationType,
precursorMassTolerance: PrecursorMassTolerance,
productMassTolerance: ProductMassTolerance,
digestionParams: digestionParamsToSave,
trimMs1Peaks: TrimMs1Peaks,
trimMsMsPeaks: TrimMsMsPeaks,
numberOfPeaksToKeepPerWindow: numPeaksToKeep,
minimumAllowedIntensityRatioToBasePeak: minimumAllowedIntensityRatioToBasePeak,
windowWidthThomsons: windowWidthThompsons,
numberOfWindows: numberOfWindows, //maybe change this some day
normalizePeaksAccrossAllWindows: normalizePeaksAccrossAllWindows, //maybe change this some day
addCompIons: addCompIonCheckBox.IsChecked.Value,
qValueOutputFilter: QValueCheckBox.IsChecked.Value ? double.Parse(QValueTextBox.Text, CultureInfo.InvariantCulture) : 1.0,
assumeOrphanPeaksAreZ1Fragments: protease.Name != "top-down",
minVariantDepth: MinVariantDepth,
maxHeterozygousVariants: MaxHeterozygousVariants);
if (classicSearchRadioButton.IsChecked.Value)
{
TheTask.SearchParameters.SearchType = SearchType.Classic;
}
else if (modernSearchRadioButton.IsChecked.Value)
{
TheTask.SearchParameters.SearchType = SearchType.Modern;
}
else //both semi and nonspecific are termed "nonspecific", because they both contain at least one nonspecific cleavage and they share the same algorithm
{
TheTask.SearchParameters.SearchType = SearchType.NonSpecific;
}
TheTask.SearchParameters.DoParsimony = checkBoxParsimony.IsChecked.Value;
TheTask.SearchParameters.NoOneHitWonders = checkBoxNoOneHitWonders.IsChecked.Value;
TheTask.SearchParameters.DoQuantification = !checkBoxNoQuant.IsChecked.Value;
//SilacLabel deconvolution
{
if (StaticSilacLabelsObservableCollection.Count == 0)
{
TheTask.SearchParameters.SilacLabels = null;
}
else
{
List <Proteomics.SilacLabel> labelsToSave = new List <Proteomics.SilacLabel>();
foreach (SilacInfoForDataGrid info in StaticSilacLabelsObservableCollection)
{
Proteomics.SilacLabel labelToAdd = info.SilacLabel[0];
//This is needed to prevent double adding of additional labels.
//A quick test is to create a silac condition with two labels, save, reopen the task, save, and reopen again.
//Without this line, the second label will be doubled (K+8)&(R+10)&(R+10)
if (labelToAdd.AdditionalLabels != null)
{
labelToAdd.AdditionalLabels.Clear();
}
for (int infoIndex = 1; infoIndex < info.SilacLabel.Count; infoIndex++)
{
labelToAdd.AddAdditionalSilacLabel(info.SilacLabel[infoIndex]);
}
labelsToSave.Add(labelToAdd);
}
TheTask.SearchParameters.SilacLabels = labelsToSave;
}
}
TheTask.SearchParameters.Normalize = checkBoxNormalize.IsChecked.Value;
TheTask.SearchParameters.MatchBetweenRuns = checkBoxMatchBetweenRuns.IsChecked.Value;
TheTask.SearchParameters.ModPeptidesAreDifferent = modPepsAreUnique.IsChecked.Value;
TheTask.SearchParameters.QuantifyPpmTol = double.Parse(peakFindingToleranceTextBox.Text, CultureInfo.InvariantCulture);
TheTask.SearchParameters.SearchTarget = checkBoxTarget.IsChecked.Value;
TheTask.SearchParameters.WriteMzId = ckbMzId.IsChecked.Value;
TheTask.SearchParameters.WriteDecoys = writeDecoyCheckBox.IsChecked.Value;
TheTask.SearchParameters.WriteContaminants = writeContaminantCheckBox.IsChecked.Value;
//TheTask.SearchParameters.OutPepXML = ckbPepXML.IsChecked.Value;
if (checkBoxDecoy.IsChecked.Value)
{
if (radioButtonReverseDecoy.IsChecked.Value)
{
TheTask.SearchParameters.DecoyType = DecoyType.Reverse;
}
else //if (radioButtonSlideDecoy.IsChecked.Value)
{
TheTask.SearchParameters.DecoyType = DecoyType.Slide;
}
}
else
{
TheTask.SearchParameters.DecoyType = DecoyType.None;
}
if (massDiffAcceptExact.IsChecked.HasValue && massDiffAcceptExact.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.Exact;
}
if (massDiffAccept1mm.IsChecked.HasValue && massDiffAccept1mm.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.OneMM;
}
if (massDiffAccept2mm.IsChecked.HasValue && massDiffAccept2mm.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.TwoMM;
}
if (massDiffAccept3mm.IsChecked.HasValue && massDiffAccept3mm.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.ThreeMM;
}
if (massDiffAccept187.IsChecked.HasValue && massDiffAccept187.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.ModOpen;
}
if (massDiffAcceptOpen.IsChecked.HasValue && massDiffAcceptOpen.IsChecked.Value)
{
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.Open;
}
if (massDiffAcceptCustom.IsChecked.HasValue && massDiffAcceptCustom.IsChecked.Value)
{
try
{
MassDiffAcceptor customMassDiffAcceptor = SearchTask.GetMassDiffAcceptor(null, MassDiffAcceptorType.Custom, customkMdacTextBox.Text);
}
catch (Exception ex)
{
MessageBox.Show("Could not parse custom mass difference acceptor: " + ex.Message, "Error", MessageBoxButton.OK, MessageBoxImage.Error);
return;
}
TheTask.SearchParameters.MassDiffAcceptorType = MassDiffAcceptorType.Custom;
TheTask.SearchParameters.CustomMdac = customkMdacTextBox.Text;
}
//determine if semi or nonspecific with a specific protease.
if (searchModeType == CleavageSpecificity.Semi || protease.CleavageSpecificity == CleavageSpecificity.Semi)
{
TheTask.SearchParameters.LocalFdrCategories = new List <FdrCategory> {
FdrCategory.FullySpecific, FdrCategory.SemiSpecific
};
}
else if (searchModeType == CleavageSpecificity.None && protease.CleavageSpecificity != CleavageSpecificity.None)
{
TheTask.SearchParameters.LocalFdrCategories = new List <FdrCategory> {
FdrCategory.FullySpecific, FdrCategory.SemiSpecific, FdrCategory.NonSpecific
};
}
else
{
TheTask.SearchParameters.LocalFdrCategories = new List <FdrCategory> {
FdrCategory.FullySpecific
};
}
// displays warning if classic search is enabled with an open search mode
if (TheTask.SearchParameters.SearchType == SearchType.Classic &&
(TheTask.SearchParameters.MassDiffAcceptorType == MassDiffAcceptorType.ModOpen || TheTask.SearchParameters.MassDiffAcceptorType == MassDiffAcceptorType.Open))
{
MessageBoxResult result = MessageBox.Show("Modern Search mode is recommended when conducting open precursor mass searches to reduce search time.\n\n" +
"Continue anyway?", "Modern search recommended", MessageBoxButton.OKCancel);
if (result == MessageBoxResult.Cancel)
{
return;
}
}
TheTask.SearchParameters.DoHistogramAnalysis = checkBoxHistogramAnalysis.IsChecked.Value;
TheTask.SearchParameters.HistogramBinTolInDaltons = double.Parse(histogramBinWidthTextBox.Text, CultureInfo.InvariantCulture);
TheTask.SearchParameters.WritePrunedDatabase = writePrunedDBCheckBox.IsChecked.Value;
SetModSelectionForPrunedDB();
TheTask.CommonParameters = commonParamsToSave;
DialogResult = true;
}
public CompactPeptide(PeptideWithSetModifications peptideWithSetModifications, FragmentationTerminus fragmentationTerminus)
{
TerminalMasses = ComputeNeutralTerminusFragments(peptideWithSetModifications, fragmentationTerminus).ToArray();
MonoisotopicMassIncludingFixedMods = peptideWithSetModifications.MonoisotopicMass;
}
public static List <ProductType> GetTerminusSpecificProductTypesFromDissociation(DissociationType dissociationType, FragmentationTerminus fragmentationTerminus)
{
if (!TerminusSpecificProductTypesFromDissociation.TryGetValue((dissociationType, fragmentationTerminus), out List <ProductType> productTypes))
{
lock (TerminusSpecificProductTypesFromDissociation)
{
var productCollection = TerminusSpecificProductTypes.ProductIonTypesFromSpecifiedTerminus[fragmentationTerminus]
.Intersect(DissociationTypeCollection.ProductsFromDissociationType[dissociationType]);
if (!TerminusSpecificProductTypesFromDissociation.TryGetValue((dissociationType, fragmentationTerminus), out productTypes))
{
productTypes = productCollection.ToList();
TerminusSpecificProductTypesFromDissociation.Add((dissociationType, fragmentationTerminus), productTypes);
}
}
}
return(productTypes);
}
private Tuple <int, PeptideWithSetModifications> Accepts(List <Product> fragments, double scanPrecursorMass, PeptideWithSetModifications peptide, FragmentationTerminus fragmentationTerminus, MassDiffAcceptor searchMode)
{
//all masses in N and CTerminalMasses are b-ion masses, which are one water away from a full peptide
int localminPeptideLength = commonParameters.DigestionParams.MinPeptideLength;
for (int i = localminPeptideLength - 1; i < fragments.Count; i++) //minus one start, because fragment 1 is at index 0
{
Product fragment = fragments[i];
double theoMass = fragment.NeutralMass - DissociationTypeCollection.GetMassShiftFromProductType(fragment.ProductType) + WaterMonoisotopicMass;
int notch = searchMode.Accepts(scanPrecursorMass, theoMass);
if (notch >= 0)
{
PeptideWithSetModifications updatedPwsm = null;
if (fragmentationTerminus == FragmentationTerminus.N)
{
int endResidue = peptide.OneBasedStartResidueInProtein + fragment.TerminusFragment.FragmentNumber - 1; //-1 for one based index
Dictionary <int, Modification> updatedMods = new Dictionary <int, Modification>();
foreach (KeyValuePair <int, Modification> mod in peptide.AllModsOneIsNterminus)
{
if (mod.Key < endResidue - peptide.OneBasedStartResidueInProtein + 3) //check if we cleaved it off, +1 for N-terminus being mod 1 and first residue being mod 2, +1 again for the -1 on end residue for one based index, +1 (again) for the one-based start residue
{
updatedMods.Add(mod.Key, mod.Value);
}
}
updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, peptide.OneBasedStartResidueInProtein, endResidue, CleavageSpecificity.Unknown, "", 0, updatedMods, 0);
}
else
{
int startResidue = peptide.OneBasedEndResidueInProtein - fragment.TerminusFragment.FragmentNumber + 1; //plus one for one based index
Dictionary <int, Modification> updatedMods = new Dictionary <int, Modification>(); //updateMods
int indexShift = startResidue - peptide.OneBasedStartResidueInProtein;
foreach (KeyValuePair <int, Modification> mod in peptide.AllModsOneIsNterminus)
{
if (mod.Key > indexShift + 1) //check if we cleaved it off, +1 for N-terminus being mod 1 and first residue being 2
{
int key = mod.Key - indexShift;
updatedMods.Add(key, mod.Value);
}
}
updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, startResidue, peptide.OneBasedEndResidueInProtein, CleavageSpecificity.Unknown, "", 0, updatedMods, 0);
}
return(new Tuple <int, PeptideWithSetModifications>(notch, updatedPwsm));
}
else if (theoMass > scanPrecursorMass)
{
break;
}
}
//if the theoretical and experimental have the same mass
if (fragments.Count > localminPeptideLength)
{
double totalMass = peptide.MonoisotopicMass;// + Constants.ProtonMass;
int notch = searchMode.Accepts(scanPrecursorMass, totalMass);
if (notch >= 0)
{
//need to update so that the cleavage specificity is recorded
PeptideWithSetModifications updatedPwsm = new PeptideWithSetModifications(peptide.Protein, peptide.DigestionParams, peptide.OneBasedStartResidueInProtein, peptide.OneBasedEndResidueInProtein, CleavageSpecificity.Unknown, "", 0, peptide.AllModsOneIsNterminus, peptide.NumFixedMods);
return(new Tuple <int, PeptideWithSetModifications>(notch, updatedPwsm));
}
}
return(new Tuple <int, PeptideWithSetModifications>(-1, null));
}
