Gptmd approach update

MetaMorpheus/EngineLayer/MetaMorpheusEngine.cs

@@ -137,11 +137,6 @@ public static List<MatchedFragmentIon> MatchFragmentIons(Ms2ScanWithSpecificMass
 
             if (scan.TheScan.MassSpectrum.XcorrProcessed && scan.TheScan.MassSpectrum.XArray.Length != 0)
             {
-                // if the spectrum has no peaks
-                if (scan.TheScan.MassSpectrum.XArray.Length == 0)
-                {
-                    return matchedFragmentIons;
-                }
 
                 for (int i = 0; i < theoreticalProducts.Count; i++)
                 {
@@ -225,7 +220,7 @@ public static List<MatchedFragmentIon> MatchFragmentIons(Ms2ScanWithSpecificMass
 
             return matchedFragmentIons;
         }
-
+        
         //Used only when user wants to generate spectral library.
         //Normal search only looks for one match ion for one fragment, and if it accepts it then it doesn't try to look for different charge states of that same fragment. 
         //But for library generation, we need find all the matched peaks with all the different charges.

MetaMorpheus/EngineLayer/ModificationAnalysis/ModificationAnalysisEngine.cs

@@ -117,7 +117,7 @@ protected override MetaMorpheusEngineResults RunSpecific()
                 if (unlocalizedFormulas.ContainsKey(representativePsm.ModsChemicalFormula))
                     unlocalizedFormulas[representativePsm.ModsChemicalFormula] += 1;
                 else
-                    unlocalizedFormulas.Add(representativePsm.ModsChemicalFormula, 1);
+                    unlocalizedFormulas.Add(representativePsm.ModsChemicalFormula, 1); 
             }
 
             myAnalysisResults.CountOfEachModSeenOnProteins = modsOnProteins.GroupBy(b => b.Item2).ToDictionary(b => b.Key, b => b.Count());

MetaMorpheus/TaskLayer/GPTMDTask/GPTMDTask.cs

@@ -13,6 +13,7 @@
 using Proteomics.ProteolyticDigestion;
 using System.Globalization;
 using Omics.Modifications;
+using System.Threading.Tasks;
 
 namespace TaskLayer
 {
@@ -30,14 +31,30 @@ public GptmdTask() : base(MyTask.Gptmd)
 
         protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask> dbFilenameList, List<string> currentRawFileList, string taskId, FileSpecificParameters[] fileSettingsList)
         {
+            MyFileManager myFileManager = new MyFileManager(true);
+            var fileSpecificCommonParams = fileSettingsList.Select(b => SetAllFileSpecificCommonParams(CommonParameters, b));
+
+            // start loading first spectra file in the background
+            Task<MsDataFile> nextFileLoadingTask = new(() => myFileManager.LoadFile(currentRawFileList[0], SetAllFileSpecificCommonParams(CommonParameters, fileSettingsList[0])));
+            nextFileLoadingTask.Start();
             LoadModifications(taskId, out var variableModifications, out var fixedModifications, out var localizeableModificationTypes);
 
+            // start loading proteins in the background
+            List<Protein> proteinList = null;
+            Task<List<Protein>> proteinLoadingTask = new(() =>
+            {
+                var proteins = LoadProteins(taskId, dbFilenameList, true, DecoyType.Reverse,
+                    localizeableModificationTypes,
+                    CommonParameters);
+                SanitizeProteinDatabase(proteins, TargetContaminantAmbiguity.RemoveContaminant);
+                return proteins;
+            });
+            proteinLoadingTask.Start();
+
             // TODO: print error messages loading GPTMD mods
             List<Modification> gptmdModifications = GlobalVariables.AllModsKnown.OfType<Modification>().Where(b => GptmdParameters.ListOfModsGptmd.Contains((b.ModificationType, b.IdWithMotif))).ToList();
             IEnumerable<Tuple<double, double>> combos = LoadCombos(gptmdModifications).ToList();
 
-            // load proteins
-            List<Protein> proteinList = LoadProteins(taskId, dbFilenameList, true, DecoyType.Reverse, localizeableModificationTypes, CommonParameters);
 
             List<SpectralMatch> allPsms = new List<SpectralMatch>();
 
@@ -62,18 +79,13 @@ protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask
             ProseCreatedWhileRunning.Append("precursor mass tolerance(s) = {" + tempSearchMode.ToProseString() + "}; ");
 
             ProseCreatedWhileRunning.Append("product mass tolerance = " + CommonParameters.ProductMassTolerance + ". ");
-            ProseCreatedWhileRunning.Append("The combined search database contained " + proteinList.Count(p => !p.IsDecoy) + " non-decoy protein entries including " + proteinList.Where(p => p.IsContaminant).Count() + " contaminant sequences. ");
 
             // start the G-PTM-D task
             Status("Running G-PTM-D...", new List<string> { taskId });
             MyTaskResults = new MyTaskResults(this)
             {
                 NewDatabases = new List<DbForTask>()
             };
-            var fileSpecificCommonParams = fileSettingsList.Select(b => SetAllFileSpecificCommonParams(CommonParameters, b));
-            HashSet<DigestionParams> ListOfDigestionParams = new HashSet<DigestionParams>(fileSpecificCommonParams.Select(p => p.DigestionParams));
-
-            MyFileManager myFileManager = new MyFileManager(true);
 
             object lock1 = new object();
             object lock2 = new object();
@@ -94,14 +106,39 @@ protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask
                 NewCollection(Path.GetFileName(origDataFile), new List<string> { taskId, "Individual Spectra Files", origDataFile });
 
                 Status("Loading spectra file...", new List<string> { taskId, "Individual Spectra Files", origDataFile });
-                MsDataFile myMsDataFile = myFileManager.LoadFile(origDataFile, combinedParams);
+
+                // ensure that the next file has finished loading from the async method
+                nextFileLoadingTask.Wait();
+                var myMsDataFile = nextFileLoadingTask.Result;
+                // if another file exists, then begin loading it in while the previous is being searched
+                if (origDataFile != currentRawFileList.Last())
+                {
+                    int nextFileIndex = spectraFileIndex + 1;
+                    nextFileLoadingTask = new Task<MsDataFile>(() => myFileManager.LoadFile(currentRawFileList[nextFileIndex], SetAllFileSpecificCommonParams(CommonParameters, fileSettingsList[nextFileIndex])));
+                    nextFileLoadingTask.Start();
+                }
                 Status("Getting ms2 scans...", new List<string> { taskId, "Individual Spectra Files", origDataFile });
                 Ms2ScanWithSpecificMass[] arrayOfMs2ScansSortedByMass = GetMs2Scans(myMsDataFile, origDataFile, combinedParams).OrderBy(b => b.PrecursorMass).ToArray();
                 myFileManager.DoneWithFile(origDataFile);
                 SpectralMatch[] allPsmsArray = new PeptideSpectralMatch[arrayOfMs2ScansSortedByMass.Length];
 
                 //spectral Library search and library generation have't applied to GPTMD yet
                 bool writeSpctralLibrary = false;
+
+                // ensure proteins are loaded in before proceeding with search
+                switch (proteinLoadingTask.IsCompleted)
+                {
+                    case true when proteinList is null: // has finished loading but not been set
+                        proteinList = proteinLoadingTask.Result;
+                        break;
+                    case true when proteinList.Any(): // has finished loading and already been set
+                        break;
+                    case false: // has not finished loading
+                        proteinLoadingTask.Wait();
+                        proteinList = proteinLoadingTask.Result;
+                        break;
+                }
+
                 new ClassicSearchEngine(allPsmsArray, arrayOfMs2ScansSortedByMass, variableModifications, fixedModifications, null, null, null, 
                     proteinList, searchMode, combinedParams, this.FileSpecificParameters, null, new List<string> { taskId, "Individual Spectra Files", origDataFile }, writeSpctralLibrary).Run();
                 allPsms.AddRange(allPsmsArray.Where(p => p != null));
@@ -110,18 +147,8 @@ protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask
             }
             ReportProgress(new ProgressEventArgs(100, "Done!", new List<string> { taskId, "Individual Spectra Files" }));
 
-            allPsms = allPsms.OrderByDescending(b => b.Score)
-                .ThenBy(b => b.BioPolymerWithSetModsMonoisotopicMass.HasValue ? Math.Abs(b.ScanPrecursorMass - b.BioPolymerWithSetModsMonoisotopicMass.Value) : double.MaxValue)
-                .GroupBy(b => new Tuple<string, int, double?>(b.FullFilePath, b.ScanNumber, b.BioPolymerWithSetModsMonoisotopicMass))
-                .Select(b => b.First()).ToList();
-
-            new FdrAnalysisEngine(allPsms, tempSearchMode.NumNotches, CommonParameters, this.FileSpecificParameters, new List<string> { taskId }).Run();
-
-            var writtenFile = Path.Combine(OutputFolder, "GPTMD_Candidates.psmtsv");
-            WritePsmsToTsv(allPsms, writtenFile, new Dictionary<string, int>());
-            FinishedWritingFile(writtenFile, new List<string> { taskId });
+            new FdrAnalysisEngine(allPsms.OrderBy(p=>p).ToList(), tempSearchMode.NumNotches, CommonParameters, this.FileSpecificParameters, new List<string> { taskId }, doPEP: false).Run();
 
-            // get file-specific precursor mass tolerances for the GPTMD engine
             var filePathToPrecursorMassTolerance = new Dictionary<string, Tolerance>();
             for (int i = 0; i < currentRawFileList.Count; i++)
             {
@@ -135,6 +162,7 @@ protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask
             }
 
             // run GPTMD engine
+            Status("Creating the GPTMD Database", new List<string> { taskId });
             var gptmdResults = (GptmdResults)new GptmdEngine(allPsms, gptmdModifications, combos, filePathToPrecursorMassTolerance, CommonParameters, this.FileSpecificParameters, new List<string> { taskId }).Run();
 
             // Stop if canceled
@@ -188,6 +216,7 @@ protected override MyTaskResults RunSpecific(string OutputFolder, List<DbForTask
                 MyTaskResults.AddTaskSummaryText("Mods types and counts:");
                 MyTaskResults.AddTaskSummaryText(string.Join(Environment.NewLine, newModsActuallyWritten.OrderByDescending(b => b.Value).Select(b => "\t" + b.Key + "\t" + b.Value)));
             }
+            Status("Done", new List<string> { taskId });
             return MyTaskResults;
         }
 

MetaMorpheus/Test/CustomFragmentationTest.cs

@@ -122,16 +122,9 @@ public static void CustomFragmentationManyTasks()
             CollectionAssert.AreEquivalent(customIons, loadedSearchTask.CommonParameters.CustomIons);
             Assert.That(loadedSearchTask.CommonParameters.DissociationType, Is.EqualTo(DissociationType.Custom));
 
-            // read gptmd and search results to ensure matched ions are correct
-            var gptmdResults = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "GPTMD", "GPTMD_Candidates.psmtsv"), out List<string> warnings);
+            var searchResults = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "Search", "AllPSMs.psmtsv"), out List<string> warnings);
             Assert.That(!warnings.Any());
-            var productIons = gptmdResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
-                .Distinct();
-            CollectionAssert.AreEquivalent(customIons, productIons);
-
-            var searchResults = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "Search", "AllPSMs.psmtsv"), out warnings);
-            Assert.That(!warnings.Any());
-            productIons = searchResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
+            var productIons = searchResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
                 .Distinct();
             CollectionAssert.AreEquivalent(customIons, productIons);
 
@@ -156,13 +149,6 @@ public static void CustomFragmentationManyTasks()
             CollectionAssert.AreEquivalent(customIons, loadedSearchTask.CommonParameters.CustomIons);
             Assert.That(loadedSearchTask.CommonParameters.DissociationType, Is.EqualTo(DissociationType.Custom));
 
-            // read gptmd and search results to ensure matched ions are correct
-            gptmdResults = PsmTsvReader.ReadTsv(Path.Combine(newOutputFolder, "GPTMD", "GPTMD_Candidates.psmtsv"), out warnings);
-            Assert.That(!warnings.Any());
-            productIons = gptmdResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
-                .Distinct();
-            CollectionAssert.AreEquivalent(customIons, productIons);
-
             searchResults = PsmTsvReader.ReadTsv(Path.Combine(newOutputFolder, "Search", "AllPSMs.psmtsv"), out warnings);
             Assert.That(!warnings.Any());
             productIons = searchResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
@@ -298,16 +284,9 @@ public static void CustomFragmentIonsManySearchTasksContainingDifferentIons()
             CollectionAssert.AreEquivalent(customIons3, loadedSearchTask3.CommonParameters.CustomIons);
             Assert.That(loadedSearchTask3.CommonParameters.DissociationType == DissociationType.Custom);
 
-            // read gptmd and search results to ensure matched ions are correct
-            var gptmdResults = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "GPTMD", "GPTMD_Candidates.psmtsv"), out List<string> warnings);
+            var searchResults1 = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "Search1", "AllPSMs.psmtsv"), out List<string> warnings);
             Assert.That(!warnings.Any());
-            var productIons = gptmdResults.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
-                .Distinct();
-            CollectionAssert.AreEquivalent(customIons2, productIons);
-
-            var searchResults1 = PsmTsvReader.ReadTsv(Path.Combine(outputFolder, "Search1", "AllPSMs.psmtsv"), out warnings);
-            Assert.That(!warnings.Any());
-            productIons = searchResults1.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
+            var productIons = searchResults1.SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
                 .Distinct();
             CollectionAssert.AreEquivalent(customIons1, productIons);
 
@@ -365,15 +344,6 @@ public static void CustomFragmentIonsManySearchTasksContainingDifferentIons()
             CollectionAssert.AreEquivalent(customIons3, loadedSearchTask3.CommonParameters.CustomIons);
             Assert.That(loadedSearchTask3.CommonParameters.DissociationType == DissociationType.Custom);
 
-            // read gptmd and search results to ensure matched ions are correct
-            gptmdResults = PsmTsvReader.ReadTsv(Path.Combine(newOutputFolder, "GPTMD", "GPTMD_Candidates.psmtsv"),
-                out warnings);
-            Assert.That(!warnings.Any());
-            productIons = gptmdResults
-                .SelectMany(p => p.MatchedIons.Select(m => m.NeutralTheoreticalProduct.ProductType))
-                .Distinct();
-            CollectionAssert.AreEquivalent(customIons2, productIons);
-
             searchResults1 =
                 PsmTsvReader.ReadTsv(Path.Combine(newOutputFolder, "Search1", "AllPSMs.psmtsv"), out warnings);
             Assert.That(!warnings.Any());