public AreaCVRefinementData(SrmDocument document, AreaCVRefinementSettings settings,
CancellationToken?token = null)
{
_settings = settings;
if (document == null || !document.Settings.HasResults)
{
return;
}
var replicates = document.MeasuredResults.Chromatograms.Count;
var areas = new List <AreaInfo>(replicates);
var annotations = AnnotationHelper.GetPossibleAnnotations(document.Settings, settings.Group, AnnotationDef.AnnotationTarget.replicate);
if (!annotations.Any() && settings.Group == null)
{
annotations = new string[] { null }
}
;
_internalData = new List <InternalData>();
var hasHeavyMods = document.Settings.PeptideSettings.Modifications.HasHeavyModifications;
var hasGlobalStandards = document.Settings.HasGlobalStandardArea;
var ms1 = settings.MsLevel == AreaCVMsLevel.precursors;
// Avoid using not-MS1 with a document that is only MS1
if (!ms1 && document.MoleculeTransitions.All(t => t.IsMs1))
{
ms1 = true;
}
double?qvalueCutoff = null;
if (ShouldUseQValues(document))
{
qvalueCutoff = _settings.QValueCutoff;
}
int?minDetections = null;
if (_settings.MinimumDetections != -1)
{
minDetections = _settings.MinimumDetections;
}
MedianInfo medianInfo = null;
if (_settings.NormalizationMethod == AreaCVNormalizationMethod.medians)
{
medianInfo = CalculateMedianAreas(document);
}
foreach (var peptideGroup in document.MoleculeGroups)
{
foreach (var peptide in peptideGroup.Molecules)
{
foreach (var transitionGroupDocNode in peptide.TransitionGroups)
{
if (_settings.PointsType == PointsTypePeakArea.decoys != transitionGroupDocNode.IsDecoy)
{
continue;
}
foreach (var a in annotations)
{
areas.Clear();
if (a != _settings.Annotation && (_settings.Group == null || _settings.Annotation != null))
{
continue;
}
foreach (var i in AnnotationHelper.GetReplicateIndices(document.Settings, _settings.Group, a))
{
if (token.HasValue && token.Value.IsCancellationRequested)
{
throw new Exception(@"Cancelled");
}
var groupChromInfo = transitionGroupDocNode.GetSafeChromInfo(i)
.FirstOrDefault(c => c.OptimizationStep == 0);
if (groupChromInfo == null)
{
continue;
}
if (qvalueCutoff.HasValue)
{
if (!(groupChromInfo.QValue.HasValue && groupChromInfo.QValue.Value < qvalueCutoff.Value))
{
continue;
}
}
if (!groupChromInfo.Area.HasValue)
{
continue;
}
var index = i;
var sumArea = transitionGroupDocNode.Transitions.Where(t =>
{
if (ms1 != t.IsMs1 || !t.ExplicitQuantitative)
{
return(false);
}
var chromInfo = t.GetSafeChromInfo(index)
.FirstOrDefault(c => c.OptimizationStep == 0);
if (chromInfo == null)
{
return(false);
}
if (_settings.Transitions == AreaCVTransitions.best)
{
return(chromInfo.RankByLevel == 1);
}
if (_settings.Transitions == AreaCVTransitions.all)
{
return(true);
}
return(chromInfo.RankByLevel <= _settings.CountTransitions);
// ReSharper disable once PossibleNullReferenceException
}).Sum(t => (double)t.GetSafeChromInfo(index).FirstOrDefault(c => c.OptimizationStep == 0).Area);
var normalizedArea = sumArea;
if (_settings.NormalizationMethod == AreaCVNormalizationMethod.medians)
{
normalizedArea /= medianInfo.Medians[i] / medianInfo.MedianMedian;
}
else if (_settings.NormalizationMethod == AreaCVNormalizationMethod.global_standards && hasGlobalStandards)
{
normalizedArea =
NormalizeToGlobalStandard(document, transitionGroupDocNode, i, sumArea);
}
else if (_settings.NormalizationMethod == AreaCVNormalizationMethod.ratio && hasHeavyMods && _settings.RatioIndex >= 0)
{
var ci = transitionGroupDocNode.GetSafeChromInfo(i).FirstOrDefault(c => c.OptimizationStep == 0);
if (ci != null)
{
var ratioValue = ci.GetRatio(_settings.RatioIndex);
if (ratioValue == null)
{
continue; // Skip the standards
}
normalizedArea = ratioValue.Ratio;
}
}
areas.Add(new AreaInfo(sumArea, normalizedArea));
}
if (qvalueCutoff.HasValue && minDetections.HasValue && areas.Count < minDetections.Value)
{
continue;
}
_settings.AddToInternalData(_internalData, areas, peptideGroup, peptide, transitionGroupDocNode, a);
}
}
}
}
Data = ImmutableList <CVData> .ValueOf(_internalData.GroupBy(i => i, (key, grouped) =>
{
var groupedArray = grouped.ToArray();
return(new CVData(
groupedArray.Select(idata => new PeptideAnnotationPair(idata.PeptideGroup, idata.Peptide, idata.TransitionGroup, idata.Annotation, idata.CV)),
key.CVBucketed, key.Area, groupedArray.Length));
}).OrderBy(d => d.CV));
}
public AreaCVRefinementData(SrmDocument document, AreaCVRefinementSettings settings,
CancellationToken token, SrmSettingsChangeMonitor progressMonitor = null)
{
_settings = settings;
if (document == null || !document.Settings.HasResults)
{
return;
}
var replicates = document.MeasuredResults.Chromatograms.Count;
var areas = new List <AreaInfo>(replicates);
var annotations = AnnotationHelper.GetPossibleAnnotations(document, settings.Group).ToArray();
if (!annotations.Any() && settings.Group == null)
{
annotations = new string[] { null }
}
;
_internalData = new List <InternalData>();
var hasHeavyMods = document.Settings.PeptideSettings.Modifications.HasHeavyModifications;
var hasGlobalStandards = document.Settings.HasGlobalStandardArea;
var ms1 = settings.MsLevel == AreaCVMsLevel.precursors;
// Avoid using not-MS1 with a document that is only MS1
if (!ms1 && document.MoleculeTransitions.All(t => t.IsMs1))
{
ms1 = true;
}
double?qvalueCutoff = null;
if (ShouldUseQValues(document))
{
qvalueCutoff = _settings.QValueCutoff;
}
int?minDetections = null;
if (_settings.MinimumDetections != -1)
{
minDetections = _settings.MinimumDetections;
}
MedianInfo medianInfo = null;
int? ratioIndex = null;
if (settings.NormalizeOption.IsRatioToLabel)
{
var isotopeLabelTypeName = (settings.NormalizeOption.NormalizationMethod as NormalizationMethod.RatioToLabel)
?.IsotopeLabelTypeName;
ratioIndex =
document.Settings.PeptideSettings.Modifications.RatioInternalStandardTypes.IndexOf(type =>
type.Name == isotopeLabelTypeName);
}
if (_settings.NormalizeOption.Is(NormalizationMethod.EQUALIZE_MEDIANS))
{
medianInfo = CalculateMedianAreas(document);
}
NormalizationData normalizationData = null;
foreach (var peptideGroup in document.MoleculeGroups)
{
foreach (var peptide in peptideGroup.Molecules)
{
if (progressMonitor != null)
{
progressMonitor.ProcessMolecule(peptide);
}
if (_settings.PointsType == PointsTypePeakArea.decoys != peptide.IsDecoy)
{
continue;
}
CalibrationCurveFitter calibrationCurveFitter = null;
CalibrationCurve calibrationCurve = null;
IEnumerable <TransitionGroupDocNode> transitionGroups;
if (_settings.NormalizeOption == NormalizeOption.CALIBRATED ||
_settings.NormalizeOption == NormalizeOption.DEFAULT)
{
if (!peptide.TransitionGroups.Any())
{
continue;
}
var peptideQuantifier = PeptideQuantifier.GetPeptideQuantifier(() =>
{
return(normalizationData = normalizationData ?? NormalizationData.GetNormalizationData(document, false, null));
}, document.Settings, peptideGroup, peptide);
calibrationCurveFitter = new CalibrationCurveFitter(peptideQuantifier, document.Settings);
transitionGroups = new[] { peptide.TransitionGroups.First() };
if (_settings.NormalizeOption == NormalizeOption.CALIBRATED)
{
calibrationCurve = calibrationCurveFitter.GetCalibrationCurve();
if (calibrationCurve == null)
{
continue;
}
}
}
else
{
transitionGroups = peptide.TransitionGroups;
}
foreach (var transitionGroupDocNode in transitionGroups)
{
foreach (var a in annotations)
{
areas.Clear();
if (!Equals(a, _settings.Annotation) && (_settings.Group == null || _settings.Annotation != null))
{
continue;
}
foreach (var replicateIndex in AnnotationHelper.GetReplicateIndices(document,
_settings.Group, a))
{
if (progressMonitor != null && progressMonitor.IsCanceled())
{
throw new OperationCanceledException();
}
token.ThrowIfCancellationRequested();
var groupChromInfo = transitionGroupDocNode.GetSafeChromInfo(replicateIndex)
.FirstOrDefault(c => c.OptimizationStep == 0);
if (groupChromInfo == null)
{
continue;
}
if (qvalueCutoff.HasValue)
{
if (!(groupChromInfo.QValue.HasValue &&
groupChromInfo.QValue.Value < qvalueCutoff.Value))
{
continue;
}
}
double sumArea, normalizedArea;
if (calibrationCurveFitter != null)
{
double?value;
if (calibrationCurve != null)
{
value = calibrationCurveFitter.GetCalculatedConcentration(calibrationCurve,
replicateIndex);
}
else
{
value = calibrationCurveFitter.GetNormalizedPeakArea(
new CalibrationPoint(replicateIndex, null));
}
if (!value.HasValue)
{
continue;
}
sumArea = value.Value;
normalizedArea = value.Value;
}
else
{
if (!groupChromInfo.Area.HasValue)
{
continue;
}
var index = replicateIndex;
sumArea = transitionGroupDocNode.Transitions.Where(t =>
{
if (ms1 != t.IsMs1 || !t.ExplicitQuantitative)
{
return(false);
}
var chromInfo = t.GetSafeChromInfo(index)
.FirstOrDefault(c => c.OptimizationStep == 0);
if (chromInfo == null)
{
return(false);
}
if (_settings.Transitions == AreaCVTransitions.best)
{
return(chromInfo.RankByLevel == 1);
}
if (_settings.Transitions == AreaCVTransitions.all)
{
return(true);
}
return(chromInfo.RankByLevel <= _settings.CountTransitions);
// ReSharper disable once PossibleNullReferenceException
}).Sum(t => (double)t.GetSafeChromInfo(index)
.FirstOrDefault(c => c.OptimizationStep == 0).Area);
normalizedArea = sumArea;
if (_settings.NormalizeOption.Is(NormalizationMethod.EQUALIZE_MEDIANS))
{
normalizedArea /= medianInfo.Medians[replicateIndex] / medianInfo.MedianMedian;
}
else if (_settings.NormalizeOption.Is(NormalizationMethod.GLOBAL_STANDARDS) &&
hasGlobalStandards)
{
normalizedArea =
NormalizeToGlobalStandard(document, transitionGroupDocNode, replicateIndex,
sumArea);
}
else if (_settings.NormalizeOption.Is(NormalizationMethod.TIC))
{
var denominator = document.Settings.GetTicNormalizationDenominator(
replicateIndex, groupChromInfo.FileId);
if (!denominator.HasValue)
{
continue;
}
normalizedArea /= denominator.Value;
}
else if (hasHeavyMods &&
_settings.NormalizeOption.NormalizationMethod is NormalizationMethod
.RatioToLabel)
{
var ci = transitionGroupDocNode.GetSafeChromInfo(replicateIndex)
.FirstOrDefault(c => c.OptimizationStep == 0);
RatioValue ratioValue = null;
if (ratioIndex.HasValue && ratioIndex.Value >= 0 &&
ratioIndex.Value < ci.Ratios.Count)
{
ratioValue = ci.Ratios[ratioIndex.Value];
}
if (ratioValue == null)
{
continue;
}
normalizedArea = ratioValue.Ratio;
}
}
areas.Add(new AreaInfo(sumArea, normalizedArea));
}
if (qvalueCutoff.HasValue && minDetections.HasValue && areas.Count < minDetections.Value)
{
continue;
}
_settings.AddToInternalData(_internalData, areas, peptideGroup, peptide, transitionGroupDocNode, a);
}
}
}
}
Data = ImmutableList <CVData> .ValueOf(_internalData.GroupBy(i => i, (key, grouped) =>
{
var groupedArray = grouped.ToArray();
return(new CVData(
groupedArray.Select(idata => new PeptideAnnotationPair(idata.PeptideGroup, idata.Peptide, idata.TransitionGroup, idata.Annotation, idata.CV)),
key.CVBucketed, key.Area, groupedArray.Length));
}).OrderBy(d => d.CV));
}