public void TestTargetDetectionWithIsomersHard()
{
// BHC
string formula3 = "C13H18ClNO";
MolecularTarget sample3 = new MolecularTarget(formula3, IonizationMethod.Protonated, "BHC");
string fileLocation3 = BHC;
CrossSectionSearchParameters parameters3 = new CrossSectionSearchParameters(testDriftTubeLength);
CrossSectionWorkfow workfow3 = new CrossSectionWorkfow(fileLocation3, "output", parameters3);
CrossSectionWorkflowResult results3 = workfow3.RunCrossSectionWorkFlow(sample3, true);
Assert.AreEqual(2, results3.IdentifiedIsomers.Count());
workfow3.Dispose();
}
public void TestSingleMoleculeWithFormula()
{
// Nicotine
// string formula = "C10H14N2";
// ImsTarget sample = new ImsTarget(1, Adduct.Protonated, formula);
// Console.WriteLine("MZ: " + 221.0594);
// string fileLocation = AcetamipridFile;
// Acetamiprid
// string formula = "C10H11ClN4";
// ImsTarget sample = new ImsTarget(1, Adduct.Deprotonated, formula);
// string fileLocation = AcetamipridFile;
// F1E
// string formula = "C15H21Cl2FN2O3";
// MolecularTarget sample = new MolecularTarget(formula, IonizationMethod.Protonated);
// string fileLocation = F1E;
// BPS Negative
// string formula = "C12H10O4S";
// MolecularTarget sample = new MolecularTarget(formula, IonizationMethod.prot);
// string fileLocation = BPSNegative;
// BPS Positive
string formula = "C12H10O4S";
MolecularTarget sample = new MolecularTarget(formula, IonizationMethod.Protonated, "BPS");
string fileLocation = BPSPostive;
CrossSectionSearchParameters parameters = new CrossSectionSearchParameters(testDriftTubeLength);
CrossSectionWorkfow workfow = new CrossSectionWorkfow(fileLocation, "output", parameters);
CrossSectionWorkflowResult result = workfow.RunCrossSectionWorkFlow(sample, true);
Assert.AreEqual(1, result.IdentifiedIsomers.Count());
Assert.LessOrEqual(Math.Abs(result.IdentifiedIsomers.First().CrossSectionalArea - 166.3012), 0.5);
workfow.Dispose();
}
public int TestTargetDetectionWithIsomersClean(string formula, IonizationMethod method, string descriptor, string fileLocation)
{
MolecularTarget sample1 = new MolecularTarget(formula, method, descriptor);
CrossSectionSearchParameters parameters1 = new CrossSectionSearchParameters(CrossSectionSearchParameters.DefaultDriftTimeToleranceInMs, CrossSectionSearchParameters.DefaultMzWindowHalfWidthInPpm,
CrossSectionSearchParameters.DefaultNumPointForSmoothing, CrossSectionSearchParameters.DefaultFeatureFilterLevel, CrossSectionSearchParameters.DefaultAbsoluteIntensityThreshold, CrossSectionSearchParameters.DefaultPeakShapeThreshold, CrossSectionSearchParameters.DefaultIsotopicThreshold, CrossSectionSearchParameters.DefaultMaxOutliers, CrossSectionSearchParameters.DefaultPeakDetectorSelection, FitlineEnum.OrdinaryLeastSquares, CrossSectionSearchParameters.DefaultMinR2, CrossSectionSearchParameters.DefaultRelativeIntensityPercentageThreshold, "png", CrossSectionSearchParameters.DefaultInsufficientFramesFraction, testDriftTubeLength, true);
CrossSectionWorkfow workfow1 = new CrossSectionWorkfow(fileLocation, "output", parameters1);
CrossSectionWorkflowResult results1 = workfow1.RunCrossSectionWorkFlow(sample1, true);
int count = results1.IdentifiedIsomers.Count();
workfow1.Dispose();
return count;
}
public void TestSingleMoleculeMzOnly()
{
// Good BPS data
double mz = 251.037804609;
string uimfFile = BPSPostive;
// Acetaminophen
// double mz = 150.0555008;
// string uimfFile = Acetaminophen;
// Nicotinefnic
// double mz = 161.10787;
// string uimfFile = NicoFile;
// Nico M+H
// double mz = 161.10787;
// string uimfFile = NicoFile;
MolecularTarget target = new MolecularTarget(mz, IonizationMethod.Protonated, "Nicotine");
CrossSectionSearchParameters parameters = new CrossSectionSearchParameters(testDriftTubeLength);
CrossSectionWorkfow workflow = new CrossSectionWorkfow(uimfFile, "output", parameters);
workflow.RunCrossSectionWorkFlow(target);
workflow.Dispose();
}
public void TestMixedSampleCrossSectionExtraction()
{
string fileLocation = @"\\proto-2\UnitTest_Files\IMSInformedTestFiles\datasets\mix\Mix1_8Oct13_Columbia_DI.uimf";
IonizationMethod method = IonizationMethod.Sodiumated;
IList<IImsTarget> targetList = new List<IImsTarget>();
targetList.Add(new PeptideTarget(12, "DGWHSWPIAHQWPQGPSAVDAAFSWEEK", 1.0));
targetList.Add(new MolecularTarget("C3H7O7P", method, "chemical A"));
targetList.Add(new MolecularTarget("C3H7O7P", method, "chemical B(A's isomer)"));
targetList.Add(new MolecularTarget("C6H14O12P2", method, "chemical C"));
targetList.Add(new MolecularTarget("C4H6O5", method, "chemical D"));
targetList.Add(new MolecularTarget("C3H4O3", method, "chemical E"));
targetList.Add(new MolecularTarget("C5H11O8P", method, "chemical F"));
targetList.Add(new MolecularTarget("C6H8O7", method, "chemical G"));
targetList.Add(new MolecularTarget("C4H6O4", method, "chemical H"));
targetList.Add(new MolecularTarget("C3H5O6P", method, "chemical I"));
targetList.Add(new MolecularTarget("C7H15O10P", method, "chemical J"));
targetList.Add(new MolecularTarget(120.5, method, "MzInDalton specified chemical L"));
Console.WriteLine("TargetList: ");
CrossSectionSearchParameters parameters = new CrossSectionSearchParameters(testDriftTubeLength);
CrossSectionWorkfow informedWorkflow = new CrossSectionWorkfow(fileLocation, "output", parameters);
IEnumerable<CrossSectionWorkflowResult> resultMap = informedWorkflow.RunCrossSectionWorkFlow(targetList, false);
informedWorkflow.Dispose();
}
/// <summary>
/// The execute finder.
/// </summary>
/// <param name="options">
/// The options.
/// </param>
/// <returns>
/// The <see cref="int"/>.
/// </returns>
private static int ExecuteFinder(FinderOptions options)
{
try
{
string uimfFile = options.InputPath; // get the UIMF file
string datasetName = Path.GetFileNameWithoutExtension(uimfFile);
string resultName = datasetName + "_" + "Result.bin";
string resultPath = Path.Combine(options.OutputPath, resultName);
string outputDirectory = options.OutputPath;
IList<string> targetList = options.TargetList;
bool verbose = options.DetailedVerbose;
if (outputDirectory == string.Empty)
{
outputDirectory = Directory.GetCurrentDirectory();
}
if (!outputDirectory.EndsWith("\\"))
{
outputDirectory += "\\";
}
if (!Directory.Exists(outputDirectory))
{
try
{
Directory.CreateDirectory(outputDirectory);
}
catch (Exception)
{
Console.WriteLine("Failed to create directory.");
throw;
}
}
// Delete the result file if it already exists
if (File.Exists(resultPath))
{
File.Delete(resultPath);
}
// Load parameters
double Mz;
CrossSectionSearchParameters searchParameters = new CrossSectionSearchParameters(
options.DriftTimeToleranceInMs,
options.PrePpm,
options.NumberOfPointsForSmoothing,
options.FeatureFilterLevel,
options.IntensityThreshold,
options.PeakShapeScoreThreshold,
options.IsotopicScoreThreshold,
options.MaxOutliers,
CrossSectionSearchParameters.DefaultPeakDetectorSelection, // No longer an option
options.RobustRegression ? FitlineEnum.IterativelyBiSquareReweightedLeastSquares : FitlineEnum.OrdinaryLeastSquares,
options.MinR2,
options.RelativeIntensityPercentageThreshold,
options.GraphicsFormat,
options.InsufficientFramesFraction,
options.DriftTubeLength,
options.UseAverageTemperature);
IFormatter formatter = new BinaryFormatter();
// If target cannot be constructed. Create a result.
IList<IImsTarget> targets = new List<IImsTarget>();
IImsTarget currentTarget = null;
IList<CrossSectionWorkflowResult> errorTargets = new List<CrossSectionWorkflowResult>();
foreach (string item in targetList)
{
foreach (string ionization in options.IonizationList)
{
try
{
// get the ionization method.
IonizationMethod method = IonizationMethodUtilities.ParseIonizationMethod(ionization.Trim());
Tuple<string, string> target = ParseTargetToken(item, datasetName);
string formula = target.Item2;
string sampleClass = target.Item1;
bool isDouble = Double.TryParse(formula, out Mz);
if (!isDouble)
{
Regex rgx = new Regex("[^a-zA-Z0-9 -]");
formula = rgx.Replace(formula, "");
}
if (!isDouble)
{
currentTarget = new MolecularTarget(formula, method, sampleClass);
targets.Add(currentTarget);
}
else
{
currentTarget = new MolecularTarget(Mz, method, sampleClass);
targets.Add(currentTarget);
}
}
catch (Exception e)
{
// In case of error creating targets, create the target error result
CrossSectionWorkflowResult informedResult = CrossSectionWorkflowResult.CreateErrorResult(currentTarget, datasetName, uimfFile, resultPath, "");
using (Stream stream = new FileStream("serialized_result.bin", FileMode.Create, FileAccess.Write, FileShare.None))
{
formatter.Serialize(stream, informedResult);
}
throw e;
}
}
}
// Preprocessing
Console.WriteLine("Start Preprocessing:");
BincCentricIndexing.IndexUimfFile(uimfFile);
// Run algorithms in IMSInformed
CrossSectionWorkfow workflow = new CrossSectionWorkfow(uimfFile, outputDirectory, searchParameters);
IList<CrossSectionWorkflowResult> results = workflow.RunCrossSectionWorkFlow(targets, verbose);
workflow.Dispose();
// Merge the target error result dictionary and other results
foreach (var pair in errorTargets)
{
results.Add(pair);
}
// Serialize the result
string binPath = Path.Combine(outputDirectory, resultName);
using (Stream stream = new FileStream(binPath, FileMode.Create, FileAccess.Write, FileShare.None))
{
formatter.Serialize(stream, results);
}
if (options.PauseWhenDone)
{
PauseProgram();
}
// Define success
foreach (CrossSectionWorkflowResult result in results)
{
if (!(result.AnalysisStatus == AnalysisStatus.Positive || result.AnalysisStatus == AnalysisStatus.Negative || result.AnalysisStatus == AnalysisStatus.NotSufficientPoints | result.AnalysisStatus == AnalysisStatus.Rejected))
{
return 1;
}
}
return 0;
}
catch (Exception e)
{
string uimfFile = options.InputPath; // get the UIMF file
string datasetName = Path.GetFileNameWithoutExtension(uimfFile);
string resultName = datasetName + "_Result.txt";
string resultPath = Path.Combine(options.OutputPath, resultName);
string outputDirectory = options.OutputPath;
if (outputDirectory == string.Empty)
{
outputDirectory = Directory.GetCurrentDirectory();
}
if (!outputDirectory.EndsWith("\\"))
{
outputDirectory += "\\";
}
if (!Directory.Exists(outputDirectory))
{
try
{
Directory.CreateDirectory(outputDirectory);
}
catch (Exception)
{
Console.WriteLine("Failed to create directory.");
throw;
}
}
// Delete the result file if it already exists
if (File.Exists(resultPath))
{
File.Delete(resultPath);
}
Console.WriteLine(e.Message);
using (StreamWriter errorFile = File.CreateText(resultPath))
{
errorFile.Write(e.Message);
errorFile.Write(e.StackTrace);
}
if (options.PauseWhenDone)
{
PauseProgram();
}
return 1;
}
}
public void TestScoring()
{
string formula = "C9H13ClN6";
string fileLocation = Cae;
MolecularTarget target = new MolecularTarget(formula, IonizationMethod.Protonated, "CAE");
Console.WriteLine("CompositionWithoutAdduct: " + target.CompositionWithoutAdduct);
Console.WriteLine("Monoisotopic ViperCompatibleMass: " + target.MonoisotopicMass);
CrossSectionSearchParameters parameters = new CrossSectionSearchParameters(driftTubeLength);
var smoother = new SavitzkyGolaySmoother(parameters.NumPointForSmoothing, 2);
CrossSectionWorkfow workflow = new CrossSectionWorkfow(fileLocation, "output", parameters);
Console.WriteLine("Ionization method: " + target.Adduct);
Console.WriteLine("Targeting centerMz: " + target.MassWithAdduct);
// Generate Theoretical Isotopic Profile
List<Peak> theoreticalIsotopicProfilePeakList = null;
if (target.CompositionWithAdduct != null)
{
string empiricalFormula = target.CompositionWithAdduct.ToPlainString();
var theoreticalFeatureGenerator = new JoshTheorFeatureGenerator();
IsotopicProfile theoreticalIsotopicProfile = theoreticalFeatureGenerator.GenerateTheorProfile(empiricalFormula, 1);
theoreticalIsotopicProfilePeakList = theoreticalIsotopicProfile.Peaklist.Cast<Peak>().ToList();
}
// Generate VoltageSeparatedAccumulatedXICs
var uimfReader = new DataReader(fileLocation);
Console.WriteLine("Input file: {0}", fileLocation);
VoltageSeparatedAccumulatedXiCs accumulatedXiCs = new VoltageSeparatedAccumulatedXiCs(uimfReader, target.MassWithAdduct, parameters.MzWindowHalfWidthInPpm, driftTubeLength);
Console.WriteLine();
// For each voltage, find 2D XIC features
foreach (VoltageGroup voltageGroup in accumulatedXiCs.Keys)
{
Console.WriteLine("Voltage group: {0} V, Frame {1}-{2}, {3:F2}K, {4:F2}Torr",
voltageGroup.MeanVoltageInVolts,
voltageGroup.FirstFrameNumber,
voltageGroup.LastFrameNumber,
voltageGroup.MeanTemperatureInKelvin,
voltageGroup.MeanPressureInTorr);
List<IntensityPoint> intensityPoints = accumulatedXiCs[voltageGroup].IntensityPoints;
List<FeatureBlob> featureBlobs = PeakFinding.FindPeakUsingWatershed(intensityPoints, smoother, parameters.FeatureFilterLevel);
List<StandardImsPeak> standardPeaks = featureBlobs.Select(featureBlob => new StandardImsPeak(featureBlob, uimfReader, voltageGroup, target.MassWithAdduct, parameters.MzWindowHalfWidthInPpm)).ToList();
// feature scorings and Target selection.
double globalMaxIntensity = IMSUtil.MaxIntensityAfterFrameAccumulation(voltageGroup, uimfReader);
// Check each XIC Peak found
foreach (var featurePeak in standardPeaks)
{
// Evaluate feature scores.
double intensityScore = FeatureScoreUtilities.IntensityScore(featurePeak, globalMaxIntensity);
double isotopicScoreAngle = FeatureScoreUtilities.IsotopicProfileScore(
featurePeak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.Angle,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreDistance = FeatureScoreUtilities.IsotopicProfileScore(
featurePeak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.EuclideanDistance,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScorePerson = FeatureScoreUtilities.IsotopicProfileScore(
featurePeak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.PearsonCorrelation,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreBhattacharyya = FeatureScoreUtilities.IsotopicProfileScore(
featurePeak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.Bhattacharyya,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreDistanceAlternative = FeatureScoreUtilities.IsotopicProfileScore(
featurePeak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.EuclideanDistanceAlternative,
globalMaxIntensity,
workflow.NumberOfScans);
double peakShapeScore = FeatureScoreUtilities.PeakShapeScore(featurePeak, workflow.uimfReader, workflow.Parameters.MzWindowHalfWidthInPpm, workflow.Parameters.DriftTimeToleranceInMs, voltageGroup, globalMaxIntensity, workflow.NumberOfScans);
// Report all features.
Console.WriteLine(" feature found at scan number {0}", featurePeak.PeakApex.DriftTimeCenterInScanNumber);
Console.WriteLine(" IntensityScore: {0}", intensityScore);
Console.WriteLine(" peakShapeScore: {0}", peakShapeScore);
Console.WriteLine(" isotopicScore - Angle: {0}", isotopicScoreAngle);
Console.WriteLine(" isotopicScore - Distance: {0}", isotopicScoreDistance);
Console.WriteLine(" isotopicScore - Distance2:{0}", isotopicScoreDistanceAlternative);
Console.WriteLine(" isotopicScore - Pearson: {0}", isotopicScorePerson);
Console.WriteLine(" isotopicScore - Bhattacharyya: {0}", isotopicScoreBhattacharyya);
Console.WriteLine();
}
Console.WriteLine();
}
workflow.Dispose();
}
public void TestFormulaPerturbance()
{
List<Tuple<string, string>> formulas = new List<Tuple<string, string>>();
// truth
formulas.Add(new Tuple<string, string>("True formula", "C12H10O4S"));
formulas.Add(new Tuple<string, string>("1 extra H", "C12H11O4S"));
formulas.Add(new Tuple<string, string>("2 extra H", "C12H12O4S"));
formulas.Add(new Tuple<string, string>("3 extra H", "C12H13O4S"));
formulas.Add(new Tuple<string, string>("3 extra H", "C12H14O4S"));
formulas.Add(new Tuple<string, string>("4 extra H", "C12H15O4S"));
formulas.Add(new Tuple<string, string>("5 extra H", "C12H16O4S"));
formulas.Add(new Tuple<string, string>("1 less H", "C12H9O4S"));
formulas.Add(new Tuple<string, string>("2 less H", "C12H8O4S"));
formulas.Add(new Tuple<string, string>("3 less H", "C12H7O4S"));
formulas.Add(new Tuple<string, string>("4 less H", "C12H6O4S"));
Console.WriteLine("[Intensity], [Distance1], [Distance2], [Angle], [Pearson], [Bucha]");
string fileLocation = BPSNegative;
CrossSectionSearchParameters parameters = new CrossSectionSearchParameters(driftTubeLength);
CrossSectionWorkfow workflow = new CrossSectionWorkfow(fileLocation, "output", parameters);
foreach (var form in formulas)
{
bool found = false;
MolecularTarget target = new MolecularTarget(form.Item2, new IonizationAdduct(IonizationMethod.Deprotonated), form.Item1);
Console.Write(form.Item1 + ": ");
var smoother = new SavitzkyGolaySmoother(parameters.NumPointForSmoothing, 2);
// Generate Theoretical Isotopic Profile
List<Peak> theoreticalIsotopicProfilePeakList = null;
if (target.CompositionWithAdduct != null)
{
string empiricalFormula = target.CompositionWithAdduct.ToPlainString();
var theoreticalFeatureGenerator = new JoshTheorFeatureGenerator();
IsotopicProfile theoreticalIsotopicProfile = theoreticalFeatureGenerator.GenerateTheorProfile(empiricalFormula, 1);
theoreticalIsotopicProfilePeakList = theoreticalIsotopicProfile.Peaklist.Cast<Peak>().ToList();
}
// Generate VoltageSeparatedAccumulatedXICs
var uimfReader = new DataReader(fileLocation);
VoltageSeparatedAccumulatedXiCs accumulatedXiCs = new VoltageSeparatedAccumulatedXiCs(uimfReader, target.MassWithAdduct, parameters.MzWindowHalfWidthInPpm, parameters.DriftTubeLengthInCm);
var voltageGroup = accumulatedXiCs.Keys.First();
// Find peaks using multidimensional peak finder.
List<IntensityPoint> intensityPoints = accumulatedXiCs[voltageGroup].IntensityPoints;
List<FeatureBlob> featureBlobs = PeakFinding.FindPeakUsingWatershed(intensityPoints, smoother, parameters.FeatureFilterLevel);
List<StandardImsPeak> standardPeaks = featureBlobs.Select(featureBlob => new StandardImsPeak(featureBlob, uimfReader, voltageGroup, target.MassWithAdduct, parameters.MzWindowHalfWidthInPpm)).ToList();
// feature scorings and Target selection.
double globalMaxIntensity = IMSUtil.MaxIntensityAfterFrameAccumulation(voltageGroup, uimfReader);
// Check each XIC Peak found
foreach (var peak in standardPeaks)
{
// Evaluate feature scores.
double intensityScore = FeatureScoreUtilities.IntensityScore(peak, globalMaxIntensity);
double isotopicScoreAngle = FeatureScoreUtilities.IsotopicProfileScore(
peak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.Angle,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreDistance = FeatureScoreUtilities.IsotopicProfileScore(
peak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.EuclideanDistance,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScorePerson = FeatureScoreUtilities.IsotopicProfileScore(
peak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.PearsonCorrelation,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreBhattacharyya = FeatureScoreUtilities.IsotopicProfileScore(
peak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.Bhattacharyya,
globalMaxIntensity,
workflow.NumberOfScans);
double isotopicScoreDistanceAlternative = FeatureScoreUtilities.IsotopicProfileScore(
peak,
workflow.uimfReader,
target,
theoreticalIsotopicProfilePeakList,
voltageGroup,
IsotopicScoreMethod.EuclideanDistanceAlternative,
globalMaxIntensity,
workflow.NumberOfScans);
double peakShapeScore = FeatureScoreUtilities.PeakShapeScore(peak, workflow.uimfReader, workflow.Parameters.MzWindowHalfWidthInPpm, workflow.Parameters.DriftTimeToleranceInMs, voltageGroup, globalMaxIntensity, workflow.NumberOfScans);
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", intensityScore);
found = true;
}
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", isotopicScoreDistance);
found = true;
}
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", isotopicScoreDistanceAlternative);
found = true;
}
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", isotopicScoreAngle);
found = true;
}
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", isotopicScorePerson);
found = true;
}
// Report all features.
if (peak.PeakApex.DriftTimeCenterInScanNumber == 115)
{
Console.Write("{0:F4} ", isotopicScoreBhattacharyya);
found = true;
}
}
if (!found)
{
Console.Write("No features");
}
Console.WriteLine();
}
// Manually dispose so it doesn't interfere with other tests.
workflow.Dispose();
}