public SrmDocument ConvertToSmallMolecules(SrmDocument document,
ConvertToSmallMoleculesMode mode = ConvertToSmallMoleculesMode.formulas,
bool invertCharges = false,
bool ignoreDecoys=false)
{
if (mode == ConvertToSmallMoleculesMode.none)
return document;
var newdoc = new SrmDocument(document.Settings);
var note = new Annotations(TestingConvertedFromProteomic, null, 1); // Mark this as a testing node so we don't sort it
newdoc = (SrmDocument)newdoc.ChangeIgnoreChangingChildren(true); // Retain copied results
foreach (var peptideGroupDocNode in document.MoleculeGroups)
{
if (!peptideGroupDocNode.IsProteomic)
{
newdoc = (SrmDocument)newdoc.Add(peptideGroupDocNode); // Already a small molecule
}
else
{
var newPeptideGroup = new PeptideGroup();
var newPeptideGroupDocNode = new PeptideGroupDocNode(newPeptideGroup,
peptideGroupDocNode.Annotations.Merge(note), peptideGroupDocNode.Name,
peptideGroupDocNode.Description, new PeptideDocNode[0],
peptideGroupDocNode.AutoManageChildren);
foreach (var mol in peptideGroupDocNode.Molecules)
{
var peptideSequence = mol.Peptide.Sequence;
// Create a PeptideDocNode with the presumably baseline charge and label
var precursorCharge = (mol.TransitionGroups.Any() ? mol.TransitionGroups.First().TransitionGroup.PrecursorCharge : 0) * (invertCharges ? -1 : 1);
var isotopeLabelType = mol.TransitionGroups.Any() ? mol.TransitionGroups.First().TransitionGroup.LabelType : IsotopeLabelType.light;
var moleculeCustomIon = ConvertToSmallMolecule(mode, document, mol, precursorCharge, isotopeLabelType);
var precursorCustomIon = moleculeCustomIon;
var newPeptide = new Peptide(moleculeCustomIon);
var newPeptideDocNode = new PeptideDocNode(newPeptide, newdoc.Settings, null, null,
null, null, mol.ExplicitRetentionTime, note, mol.Results, new TransitionGroupDocNode[0],
mol.AutoManageChildren);
foreach (var transitionGroupDocNode in mol.TransitionGroups)
{
if (transitionGroupDocNode.IsDecoy)
{
if (ignoreDecoys)
continue;
throw new Exception("There is no translation from decoy to small molecules"); // Not L10N
}
if (transitionGroupDocNode.TransitionGroup.PrecursorCharge != Math.Abs(precursorCharge) ||
!Equals(isotopeLabelType, transitionGroupDocNode.TransitionGroup.LabelType))
{
// Different charges or labels mean different ion formulas
precursorCharge = transitionGroupDocNode.TransitionGroup.PrecursorCharge * (invertCharges ? -1 : 1);
isotopeLabelType = transitionGroupDocNode.TransitionGroup.LabelType;
precursorCustomIon = ConvertToSmallMolecule(mode, document, mol, precursorCharge, isotopeLabelType);
}
var newTransitionGroup = new TransitionGroup(newPeptide, precursorCustomIon, precursorCharge, isotopeLabelType);
// Remove any library info, since for the moment at least small molecules don't support this and it won't roundtrip
var resultsNew = RemoveTransitionGroupChromInfoLibraryInfo(transitionGroupDocNode);
var newTransitionGroupDocNode = new TransitionGroupDocNode(newTransitionGroup,
transitionGroupDocNode.Annotations.Merge(note), document.Settings,
null, null, transitionGroupDocNode.ExplicitValues, resultsNew, null,
transitionGroupDocNode.AutoManageChildren);
var mzShift = invertCharges ? 2.0 * BioMassCalc.MassProton : 0; // We removed hydrogen rather than added
Assume.IsTrue((Math.Abs(newTransitionGroupDocNode.PrecursorMz + mzShift - transitionGroupDocNode.PrecursorMz) - Math.Abs(transitionGroupDocNode.TransitionGroup.PrecursorCharge * BioMassCalc.MassElectron)) <= 1E-5);
foreach (var transition in transitionGroupDocNode.Transitions)
{
double mass = 0;
var transitionCharge = transition.Transition.Charge * (invertCharges ? -1 : 1);
var ionType = IonType.custom;
CustomIon transitionCustomIon;
double mzShiftTransition = 0;
if (transition.Transition.IonType == IonType.precursor)
{
ionType = IonType.precursor;
transitionCustomIon = new DocNodeCustomIon(precursorCustomIon.Formula,
string.IsNullOrEmpty(precursorCustomIon.Formula) ? precursorCustomIon.MonoisotopicMass : (double?) null,
string.IsNullOrEmpty(precursorCustomIon.Formula) ? precursorCustomIon.AverageMass : (double?) null,
SmallMoleculeNameFromPeptide(peptideSequence, transitionCharge));
mzShiftTransition = invertCharges ? 2.0 * BioMassCalc.MassProton : 0; // We removed hydrogen rather than added
}
else if (transition.Transition.IonType == IonType.custom)
{
transitionCustomIon = transition.Transition.CustomIon;
mass = transitionCustomIon.MonoisotopicMass;
}
else
{
// TODO - try to get fragment formula?
mass = BioMassCalc.CalculateIonMassFromMz(transition.Mz, transition.Transition.Charge);
transitionCustomIon = new DocNodeCustomIon(mass, mass,// We can't really get at mono vs average mass from m/z, but for test purposes this is fine
transition.Transition.FragmentIonName);
}
if (mode == ConvertToSmallMoleculesMode.masses_and_names)
{
// Discard the formula if we're testing the use of mass-with-names (for matching in ratio calcs) target specification
transitionCustomIon = new DocNodeCustomIon(transitionCustomIon.MonoisotopicMass, transitionCustomIon.AverageMass,
transition.Transition.FragmentIonName);
}
else if (mode == ConvertToSmallMoleculesMode.masses_only)
{
// Discard the formula and name if we're testing the use of mass-only target specification
transitionCustomIon = new DocNodeCustomIon(transitionCustomIon.MonoisotopicMass, transitionCustomIon.AverageMass);
}
var newTransition = new Transition(newTransitionGroup, ionType,
null, transition.Transition.MassIndex, transition.Transition.Charge * (invertCharges ? -1 : 1), null,
transitionCustomIon);
if (ionType == IonType.precursor)
{
mass = document.Settings.GetFragmentMass(transitionGroupDocNode.TransitionGroup.LabelType, null, newTransition, newTransitionGroupDocNode.IsotopeDist);
}
var newTransitionDocNode = new TransitionDocNode(newTransition, transition.Annotations.Merge(note),
null, mass, transition.IsotopeDistInfo, null,
transition.Results);
Assume.IsTrue((Math.Abs(newTransitionDocNode.Mz + mzShiftTransition - transition.Mz) - Math.Abs(transitionGroupDocNode.TransitionGroup.PrecursorCharge * BioMassCalc.MassElectron)) <= 1E-5, String.Format("unexpected mz difference {0}-{1}={2}", newTransitionDocNode.Mz , transition.Mz, newTransitionDocNode.Mz - transition.Mz)); // Not L10N
newTransitionGroupDocNode =
(TransitionGroupDocNode)newTransitionGroupDocNode.Add(newTransitionDocNode);
}
if (newPeptideDocNode != null)
newPeptideDocNode = (PeptideDocNode)newPeptideDocNode.Add(newTransitionGroupDocNode);
}
newPeptideGroupDocNode =
(PeptideGroupDocNode)newPeptideGroupDocNode.Add(newPeptideDocNode);
}
newdoc = (SrmDocument)newdoc.Add(newPeptideGroupDocNode);
}
}
// No retention time prediction for small molecules (yet?)
newdoc = newdoc.ChangeSettings(newdoc.Settings.ChangePeptideSettings(newdoc.Settings.PeptideSettings.ChangePrediction(
newdoc.Settings.PeptideSettings.Prediction.ChangeRetentionTime(null))));
return newdoc;
}
public static DocNodeCustomIon ConvertToSmallMolecule(ConvertToSmallMoleculesMode mode,
SrmDocument document, PeptideDocNode nodePep, int precursorCharge = 0, IsotopeLabelType isotopeLabelType = null)
{
// We're just using this masscalc to get the ion formula, so mono vs average doesn't matter
isotopeLabelType = isotopeLabelType ?? IsotopeLabelType.light;
var peptideSequence = nodePep.Peptide.Sequence;
var masscalc = document.Settings.TryGetPrecursorCalc(isotopeLabelType, nodePep.ExplicitMods) ?? new SequenceMassCalc(MassType.Monoisotopic);
// Determine the molecular formula of the charged/labeled peptide
var moleculeFormula = masscalc.GetIonFormula(peptideSequence, precursorCharge);
var moleculeCustomIon = new DocNodeCustomIon(moleculeFormula,
SmallMoleculeNameFromPeptide(peptideSequence, precursorCharge));
if (mode == ConvertToSmallMoleculesMode.masses_only)
{
// No formulas or names, just masses - see how we handle that
moleculeCustomIon = new DocNodeCustomIon(moleculeCustomIon.MonoisotopicMass,
moleculeCustomIon.AverageMass);
}
else if (mode == ConvertToSmallMoleculesMode.masses_and_names)
{
// Just masses and names - see how we handle that
moleculeCustomIon = new DocNodeCustomIon(moleculeCustomIon.MonoisotopicMass,
moleculeCustomIon.AverageMass, moleculeCustomIon.Name);
}
return moleculeCustomIon;
}