Пример #1
0
        public override void Execute(ResultCollection resultList)
        {
            Check.Require(resultList.CurrentTargetedResult is SipperLcmsTargetedResult, "Sipper Quantifier only works on Sipper-type result objects");
            Check.Require(resultList.Run.CurrentMassTag != null, this.Name + " failed; CurrentMassTag is empty");
            Check.Require(resultList.Run.CurrentMassTag.IsotopicProfile != null, this.Name + " failed; Theor isotopic profile is empty. Run a TheorFeatureGenerator");


            var result = (SipperLcmsTargetedResult)resultList.CurrentTargetedResult;

            result.AreaUnderDifferenceCurve = -9999;
            result.AreaUnderRatioCurve      = -9999;



            RatioVals.Xvalues = new double[] { 1, 2, 3, 4, 5, 6, 7 };
            RatioVals.Yvalues = new double[] { 0, 0, 0, 0, 0, 0, 0 };

            RatioLogVals.Xvalues = new double[] { 1, 2, 3, 4, 5, 6, 7 };
            RatioLogVals.Yvalues = new double[] { 0, 0, 0, 0, 0, 0, 0 };

            ChromatogramRSquaredVals.Clear();


            Check.Require(result != null, "No MassTagResult has been generated for CurrentMassTag");

            if (result.IsotopicProfile == null || result.IsotopicProfile.Peaklist == null || result.IsotopicProfile.Peaklist.Count < 2)
            {
                return;
            }


            var theorUnlabelledIso = resultList.Run.CurrentMassTag.IsotopicProfile.CloneIsotopicProfile();

            IsotopicProfileUtilities.NormalizeIsotopicProfile(theorUnlabelledIso);

            //PeakUtilities.TrimIsotopicProfile(unlabeledIso, 0.001);



            var sb = new StringBuilder();

            sb.Append(result.Target.ID + "\t" + result.Target.MZ.ToString("0.0000") + "\t" + result.Target.ChargeState +
                      "-----------------------------\n");


            var indexMostAbundantTheorPeak = theorUnlabelledIso.GetIndexOfMostIntensePeak();

            NormalizedIso = result.IsotopicProfile.CloneIsotopicProfile();
            IsotopicProfileUtilities.NormalizeIsotopicProfileToSpecificPeak(NormalizedIso, indexMostAbundantTheorPeak);

            //            return;


            if (result.Flags.Count > 0)
            {
                var flagstring = "";

                foreach (var resultFlag in result.Flags)
                {
                    flagstring += resultFlag.Description + ";";
                }

                result.ErrorDescription = flagstring.TrimEnd(';');
                result.FailedResult     = true;
                if (flagstring.Contains("PeakToTheLeft"))
                {
                    result.FailureType = Globals.TargetedResultFailureType.DeisotopingProblemDetected;
                }
                else
                {
                    result.FailureType = Globals.TargetedResultFailureType.QuantifierFailure;
                }
            }


            var resultPassesMinimalCriteria = (result.Score < MaximumFitScoreForFurtherProcessing && result.Flags.Count == 0);



            if (resultPassesMinimalCriteria)
            {
                //------------------------------------- Get chromatogramCorrelation data -------------------------------

                if (IsChromatogramCorrelationPerformed)
                {
                    GetChromatogramCorrelationData(result);
                }



                NormalizedAdjustedIso = NormalizedIso.CloneIsotopicProfile();

                //this is experimental!!  it attempts to correct the problems caused by Orbitraps on isotopic profile intensities
                //UpdateIsoIntensitiesUsingChromCorrData(result.ChromCorrelationData, NormalizedAdjustedIso);


                //----------------- create ratio data -------------------------------------------------------
                var ratioData = NormalizedAdjustedIso.CloneIsotopicProfile();
                for (var i = 0; i < NormalizedIso.Peaklist.Count; i++)
                {
                    if (i < theorUnlabelledIso.Peaklist.Count && theorUnlabelledIso.Peaklist[i].Height > MinimumRelativeIntensityForRatioCalc)
                    {
                        ratioData.Peaklist[i].Height = (NormalizedIso.Peaklist[i].Height / theorUnlabelledIso.Peaklist[i].Height - 1);
                    }
                    else
                    {
                        ratioData.Peaklist[i].Height = 0;
                    }
                }

                //trim off zeros from ratio data
                for (var i = ratioData.Peaklist.Count - 1; i >= 0; i--)
                {
                    if (ratioData.Peaklist[i].Height == 0)
                    {
                        ratioData.Peaklist.RemoveAt(i);
                    }
                    else
                    {
                        break;
                    }
                }

                var xvals = ratioData.Peaklist.Select((p, i) => new { peak = p, index = i }).Select(n => (double)n.index).ToList();
                var yvals = ratioData.Peaklist.Select(p => (double)p.Height).ToList();
                result.AreaUnderRatioCurve = yvals.Sum();

                RatioVals.Xvalues = xvals.ToArray();
                RatioVals.Yvalues = yvals.ToArray();


                GetLinearRegressionData(result, xvals, yvals);



                //------------- subtract unlabelled profile from normalized profile ----------------------
                var subtractedIsoData = NormalizedAdjustedIso.CloneIsotopicProfile();
                for (var i = 0; i < subtractedIsoData.Peaklist.Count; i++)
                {
                    float intensityTheorPeak = 0;
                    if (i < theorUnlabelledIso.Peaklist.Count)
                    {
                        intensityTheorPeak = theorUnlabelledIso.Peaklist[i].Height;
                    }


                    var subtractedIntensity = subtractedIsoData.Peaklist[i].Height - intensityTheorPeak;
                    if (subtractedIntensity < 0)
                    {
                        subtractedIntensity = 0;
                    }

                    subtractedIsoData.Peaklist[i].Height = subtractedIntensity;
                }


                result.AreaUnderDifferenceCurve = subtractedIsoData.Peaklist.Select(p => p.Height).Sum();
                result.NumCarbonsLabelled       = calculateNumCarbonsFromSubtractedProfile(subtractedIsoData);


                //-------------- calculate Label Distribution ------------------------------------------------
                double[] numLabelVals;
                double[] labelDistributionVals;

                var theorIntensityVals = theorUnlabelledIso.Peaklist.Select(p => (double)p.Height).ToList();
                var normalizedCorrectedIntensityVals = NormalizedAdjustedIso.Peaklist.Select(p => (double)p.Height).ToList();

                var numRightPads = 3;
                _labelingDistributionCalculator.CalculateLabelingDistribution(theorIntensityVals, normalizedCorrectedIntensityVals,
                                                                              LabeldistCalcIntensityThreshold,
                                                                              LabeldistCalcIntensityThreshold,
                                                                              out numLabelVals,
                                                                              out labelDistributionVals, true, true, 0, numRightPads, 0, 0);


                //negative distribution values are zeroed out. And, then the remaining values are adjusted such that they add up to 1.
                result.LabelDistributionVals = AdjustLabelDistributionVals(labelDistributionVals);


                double distFractionUnlabelled, distFractionLabelled, distAverageLabelsIncorporated;
                _labelingDistributionCalculator.OutputLabelingInfo(result.LabelDistributionVals, out distFractionUnlabelled,
                                                                   out distFractionLabelled,
                                                                   out distAverageLabelsIncorporated);



                //-------------- make calculations using inputs from chrom correlation data -------------------



                HighQualitySubtractedProfile = GetIsoDataPassingChromCorrelation(result.ChromCorrelationData, subtractedIsoData);

                var highQualityRatioProfileData = GetIsoDataPassingChromCorrelation(result.ChromCorrelationData, ratioData);

                if (highQualityRatioProfileData.Peaklist != null && highQualityRatioProfileData.Peaklist.Count > 0)
                {
                    result.AreaUnderDifferenceCurve = HighQualitySubtractedProfile.Peaklist.Select(p => p.Height).Sum();
                }
                else
                {
                    result.AreaUnderDifferenceCurve = 0;
                }

                if (HighQualitySubtractedProfile.Peaklist != null && HighQualitySubtractedProfile.Peaklist.Count > 0)
                {
                    result.AreaUnderRatioCurveRevised = highQualityRatioProfileData.Peaklist.Select(p => p.Height).Sum();
                }
                else
                {
                    result.AreaUnderRatioCurveRevised = 0;
                }


                var numCarbonsLabelled = GetNumCarbonsLabelledUsingAverageMassDifferences(theorUnlabelledIso,
                                                                                          HighQualitySubtractedProfile);



                //result.NumCarbonsLabelled = numCarbonsLabelled;
                result.NumCarbonsLabelled = distAverageLabelsIncorporated;

                var numCarbons = result.Target.GetAtomCountForElement("C");

                result.PercentCarbonsLabelled = (result.NumCarbonsLabelled / numCarbons) * 100;
                result.PercentPeptideLabelled = distFractionLabelled * 100;

                //if (HighQualitySubtractedProfile.Peaklist != null && HighQualitySubtractedProfile.Peaklist.Count > 0)
                //{
                //    result.PercentPeptideLabelled = HighQualitySubtractedProfile.Peaklist.Max(p => p.Height) * 100;
                //}
                //else
                //{
                //    result.PercentPeptideLabelled = 0;
                //}

                result.NumHighQualityProfilePeaks = highQualityRatioProfileData.Peaklist != null
                                                        ? highQualityRatioProfileData.Peaklist.Count
                                                        : 0;

                //Console.WriteLine();
                //Console.WriteLine(result);
                //foreach (var val in ChromatogramRSquaredVals)
                //{
                //    Console.WriteLine(val);
                //}
            }
            else
            {
                result.FailedResult = true;

                if (result.FailureType == Globals.TargetedResultFailureType.None)
                {
                    result.FailureType = Globals.TargetedResultFailureType.MinimalCriteriaNotMet;
                }
            }
        }
Пример #2
0
        public override void Execute(ResultCollection resultList)
        {
            Check.Require(resultList.CurrentTargetedResult is SipperLcmsTargetedResult, "Sipper Quantifier only works on Sipper-type result objects");
            Check.Require(resultList.Run.CurrentMassTag != null, this.Name + " failed; CurrentMassTag is empty");
            Check.Require(resultList.Run.CurrentMassTag.IsotopicProfile != null, this.Name + " failed; Theor isotopic profile is empty. Run a TheorFeatureGenerator");

            ResetQuantifierData();


            var result = (SipperLcmsTargetedResult)resultList.CurrentTargetedResult;

            result.AreaUnderDifferenceCurve = -9999;
            result.AreaUnderRatioCurve      = -9999;

            RatioVals.Xvalues = new double[] { 1, 2, 3, 4, 5, 6, 7 };
            RatioVals.Yvalues = new double[] { 0, 0, 0, 0, 0, 0, 0 };

            ChromatogramRSquaredVals.Clear();
            FitScoreData.Clear();


            Check.Require(result != null, "No MassTagResult has been generated for CurrentMassTag");

            if (result.IsotopicProfile == null || result.IsotopicProfile.Peaklist == null || result.IsotopicProfile.Peaklist.Count < 2)
            {
                return;
            }


            var theorUnlabelledIso = resultList.Run.CurrentMassTag.IsotopicProfile.CloneIsotopicProfile();

            IsotopicProfileUtilities.NormalizeIsotopicProfile(theorUnlabelledIso);

            //PeakUtilities.TrimIsotopicProfile(unlabeledIso, 0.001);

            var indexOfCorrespondingObservedPeak = PeakUtilities.getIndexOfClosestValue(result.IsotopicProfile.Peaklist,
                                                                                        theorUnlabelledIso.getMostIntensePeak().XValue, 0, result.IsotopicProfile.Peaklist.Count - 1, 0.1);

            NormalizedIso = result.IsotopicProfile.CloneIsotopicProfile();


            if (indexOfCorrespondingObservedPeak >= 0)
            {
                IsotopicProfileUtilities.NormalizeIsotopicProfileToSpecificPeak(NormalizedIso, indexOfCorrespondingObservedPeak);
            }
            else
            {
                IsotopicProfileUtilities.NormalizeIsotopicProfile(NormalizedIso);
            }


            //insert zero intensity peaks into observed



            //            return;


            if (result.Flags.Count > 0)
            {
                var flagstring = "";

                foreach (var resultFlag in result.Flags)
                {
                    flagstring += resultFlag.Description + ";";
                }

                result.ErrorDescription = flagstring.TrimEnd(';');
                result.FailedResult     = true;
                if (flagstring.Contains("PeakToTheLeft"))
                {
                    result.FailureType = Globals.TargetedResultFailureType.DeisotopingProblemDetected;
                }
                else
                {
                    result.FailureType = Globals.TargetedResultFailureType.QuantifierFailure;
                }
            }


            var resultPassesMinimalCriteria = (result.Score < MaximumFitScoreForFurtherProcessing && result.Flags.Count == 0);

            if (resultPassesMinimalCriteria)
            {
                //------------------------------------- Get chromatogramCorrelation data -------------------------------

                if (IsChromatogramCorrelationPerformed)
                {
                    GetChromatogramCorrelationData(result);
                }

                NormalizedAdjustedIso = NormalizedIso.CloneIsotopicProfile();

                //this is experimental!!  it attempts to correct the problems caused by Orbitraps on isotopic profile intensities
                //UpdateIsoIntensitiesUsingChromCorrData(result.ChromCorrelationData, NormalizedAdjustedIso);


                //----------------- create ratio data -------------------------------------------------------
                var ratioData = NormalizedAdjustedIso.CloneIsotopicProfile();
                for (var i = 0; i < NormalizedIso.Peaklist.Count; i++)
                {
                    if (i < theorUnlabelledIso.Peaklist.Count && theorUnlabelledIso.Peaklist[i].Height > MinimumRelativeIntensityForRatioCalc)
                    {
                        ratioData.Peaklist[i].Height = (NormalizedIso.Peaklist[i].Height / theorUnlabelledIso.Peaklist[i].Height - 1);
                    }
                    else
                    {
                        ratioData.Peaklist[i].Height = 0;
                    }
                }

                //trim off zeros from ratio data
                for (var i = ratioData.Peaklist.Count - 1; i >= 0; i--)
                {
                    if (ratioData.Peaklist[i].Height == 0)
                    {
                        ratioData.Peaklist.RemoveAt(i);
                    }
                    else
                    {
                        break;
                    }
                }

                var xvals = ratioData.Peaklist.Select((p, i) => new { peak = p, index = i }).Select(n => (double)n.index).ToList();
                var yvals = ratioData.Peaklist.Select(p => (double)p.Height).ToList();
                result.AreaUnderRatioCurve = yvals.Sum();

                RatioVals.Xvalues = xvals.ToArray();
                RatioVals.Yvalues = yvals.ToArray();


                //NOTE:  Sept 23, 2013 - the 'R is no longer used.
                result.RSquaredValForRatioCurve = GetLinearRegressionData(result, xvals, yvals);



                //------------- subtract unlabelled profile from normalized profile ----------------------
                var subtractedIsoData = NormalizedAdjustedIso.CloneIsotopicProfile();
                for (var i = 0; i < subtractedIsoData.Peaklist.Count; i++)
                {
                    float intensityTheorPeak = 0;
                    if (i < theorUnlabelledIso.Peaklist.Count)
                    {
                        intensityTheorPeak = theorUnlabelledIso.Peaklist[i].Height;
                    }


                    var subtractedIntensity = subtractedIsoData.Peaklist[i].Height - intensityTheorPeak;
                    if (subtractedIntensity < 0)
                    {
                        subtractedIntensity = 0;
                    }

                    subtractedIsoData.Peaklist[i].Height = subtractedIntensity;
                }

                result.AreaUnderDifferenceCurve = subtractedIsoData.Peaklist.Select(p => p.Height).Sum();



                //----------- get data for the subtracted, labeled isotopic profile------------------------

                var peaksForLabeledIsoQuant = new List <Peak>(subtractedIsoData.Peaklist.Where(p => p.Height > 0));


                // var isoFromPartialLabelingQuantifier = _partialLabelingQuantifier.FindBestLabeledProfile(result.Target, peaksForLabeledIsoQuant);
                //FitScoreData = _partialLabelingQuantifier.FitScoreData;

                //result.FitScoreLabeledProfile = isoFromPartialLabelingQuantifier.IsotopicProfile == null ? 1.00d : isoFromPartialLabelingQuantifier.IsotopicProfile.Score;
                //result.PercentCarbonsLabelled = isoFromPartialLabelingQuantifier.PercentLabeling;

                //int numCarbons = result.Target.GetAtomCountForElement("C");
                //result.NumCarbonsLabelled = result.PercentCarbonsLabelled * numCarbons / 100;

                //StringBuilder sb = new StringBuilder();
                //sb.Append(result.Target.ID + "\t" + result.Target.MZ.ToString("0.0000") + "\t" + result.Target.ChargeState +
                //          "-----------------------------\n");

                //int counter = 0;
                //foreach (var fsData in _partialLabelingQuantifier.FitScoreData)
                //{
                //    sb.Append(fsData.Key + "\t" + fsData.Value.ToString("0.000") + "\n");
                //    counter++;
                //}

                //Console.WriteLine(sb.ToString());


                //-------------- make calculations using inputs from chrom correlation data -------------------

                HighQualitySubtractedProfile = GetIsoDataPassingChromCorrelation(result.ChromCorrelationData, subtractedIsoData);


                var contiguousnessScore = GetContiguousnessScore(HighQualitySubtractedProfile);
                result.ContiguousnessScore = contiguousnessScore;

                //GORD ------------- note this section is a duplicate of the above....  choose one or the other ------------------------
                //Feb 26, 2013...  I processed the results and these look really good. ROC curve nice
                peaksForLabeledIsoQuant = new List <Peak>(HighQualitySubtractedProfile.Peaklist.Where(p => p.Height > 0));



                //calculate labeled fit score
                var isoFromPartialLabelingQuantifier = _partialLabelingQuantifier.FindBestLabeledProfile(result.Target, peaksForLabeledIsoQuant);
                FitScoreData = _partialLabelingQuantifier.FitScoreData;

                result.FitScoreLabeledProfile = isoFromPartialLabelingQuantifier.IsotopicProfile == null ? 1.00d : isoFromPartialLabelingQuantifier.IsotopicProfile.Score;
                result.PercentCarbonsLabelled = isoFromPartialLabelingQuantifier.PercentLabeling;

                var numCarbons = result.Target.GetAtomCountForElement("C");
                result.NumCarbonsLabelled = result.PercentCarbonsLabelled * numCarbons / 100;
                //end of section --------------------------------------------------------------------------


                //-------------- calculate Label Distribution ------------------------------------------------
                // see Chik et al:  http://pubs.acs.org/doi/abs/10.1021/ac050988l ; Also see Sipper paper.
                double[] numLabelVals;
                double[] labelDistributionVals;

                var theorIntensityVals = theorUnlabelledIso.Peaklist.Select(p => (double)p.Height).ToList();

                if (isoFromPartialLabelingQuantifier.IsotopicProfile != null)
                {
                    var normalizedCorrectedIntensityVals = NormalizedAdjustedIso.Peaklist.Select(p => (double)p.Height).ToList();

                    var numRightPads = 3;
                    _labelingDistributionCalculator.CalculateLabelingDistribution(theorIntensityVals, normalizedCorrectedIntensityVals,
                                                                                  LabeldistCalcIntensityThreshold,
                                                                                  LabeldistCalcIntensityThreshold,
                                                                                  out numLabelVals,
                                                                                  out labelDistributionVals, true, true, 0, numRightPads, 0, 0);


                    //negative distribution values are zeroed out. And, then the remaining values are adjusted such that they add up to 1.
                    result.LabelDistributionVals = AdjustLabelDistributionVals(labelDistributionVals);


                    double distFractionUnlabelled, distFractionLabelled, distAverageLabelsIncorporated;
                    _labelingDistributionCalculator.OutputLabelingInfo(result.LabelDistributionVals, out distFractionUnlabelled,
                                                                       out distFractionLabelled,
                                                                       out distAverageLabelsIncorporated);

                    result.PercentPeptideLabelled = distFractionLabelled * 100;
                }
                else
                {
                    result.PercentCarbonsLabelled = 0;
                }

                var highQualityRatioProfileData = GetIsoDataPassingChromCorrelation(result.ChromCorrelationData, ratioData);

                if (highQualityRatioProfileData.Peaklist != null && highQualityRatioProfileData.Peaklist.Count > 0)
                {
                    result.AreaUnderDifferenceCurve = HighQualitySubtractedProfile.Peaklist.Select(p => p.Height).Sum();
                }
                else
                {
                    result.AreaUnderDifferenceCurve = 0;
                }

                if (HighQualitySubtractedProfile.Peaklist != null && HighQualitySubtractedProfile.Peaklist.Count > 0)
                {
                    result.AreaUnderRatioCurveRevised = highQualityRatioProfileData.Peaklist.Select(p => p.Height).Sum();
                }
                else
                {
                    result.AreaUnderRatioCurveRevised = 0;
                }

                result.NumHighQualityProfilePeaks = highQualityRatioProfileData.Peaklist != null
                                                      ? highQualityRatioProfileData.Peaklist.Count
                                                      : 0;
            }
            else
            {
                result.FailedResult = true;

                if (result.FailureType == Globals.TargetedResultFailureType.None)
                {
                    result.FailureType = Globals.TargetedResultFailureType.MinimalCriteriaNotMet;
                }
            }
        }