Fix for a "polarity mismatch" exception when searching for nearest precursor m/z match in a mixed polarity document... (#3383)

* Fix for a "polarity mismatch" exception when searching for nearest precursor m/z match in a mixed polarity document when the m/z is negative and has greater absolute value than any negative precursor m/z.

Reported by user Paul

Author: bspratt

pwiz_tools/Skyline/Model/Results/PeptideFinder.cs

@@ -18,7 +18,6 @@
  */
 using System;
 using System.Collections.Generic;
-using System.Collections;
 using pwiz.Common.Chemistry;
 
 namespace pwiz.Skyline.Model.Results
@@ -61,22 +60,40 @@ public PeptideDocNode FindPeptide(SignedMz precursorMz)
             // Find closest precursor Mz match.
             var lookup = new PeptidePrecursorMz(null, precursorMz);
             int i = _precursorMzPeptideList.BinarySearch(lookup, PeptidePrecursorMz.COMPARER);
-            if (i < 0)
+            if (i >= 0)
             {
-                i = ~i;
-                if (i >= _precursorMzPeptideList.Count)
-                    i = _precursorMzPeptideList.Count - 1;
-                else if (i > 0 &&
-                    precursorMz - _precursorMzPeptideList[i - 1].PrecursorMz <
-                    _precursorMzPeptideList[i].PrecursorMz - precursorMz)
-                    i--;
+                return _precursorMzPeptideList[i].NodePeptide; // Exact match
             }
-            var closestMatch = _precursorMzPeptideList[i];
 
-            // Return color seed only if the match is within allowed tolerance.
-            return Math.Abs(closestMatch.PrecursorMz - precursorMz) > _mzMatchTolerance
-                ? null
-                : closestMatch.NodePeptide;
+            // BinarySearch returns bitwise complement of the index of the next larger element,
+            // but the closest match might be the element we just passed.  Also, if precursor Mz is negative,
+            // we have to make sure search hasn't crossed over into positive territory. (SignedMz sorts
+            // negative values before positive ones e.g. -100, -200, 100, 200)
+            i = ~i; 
+            PeptidePrecursorMz closestMatch = null;
+            var closestDistance = double.MaxValue;
+            for (var candidateIndex = i - 1; candidateIndex <= i; candidateIndex++)
+            {
+                if (candidateIndex < 0 || candidateIndex >= _precursorMzPeptideList.Count)
+                {
+                    continue;
+                }
+                var candidate = _precursorMzPeptideList[candidateIndex];
+                if (candidate.PrecursorMz.IsNegative != precursorMz.IsNegative)
+                {
+                    continue;
+                }
+
+                var distance = Math.Abs(candidate.PrecursorMz - precursorMz);
+                if (distance < closestDistance)
+                {
+                    closestMatch = candidate;
+                    closestDistance = distance;
+                }
+            }
+
+            // Return only if the match is within allowed tolerance.
+            return closestDistance > _mzMatchTolerance ? null : closestMatch?.NodePeptide;
         }
 
         private sealed class PeptidePrecursorMz
@@ -97,10 +114,15 @@ public class MzComparer : IComparer<PeptidePrecursorMz>
                 public int Compare(PeptidePrecursorMz p1, PeptidePrecursorMz p2)
                 {
                     // ReSharper disable PossibleNullReferenceException
-                    return Comparer.Default.Compare(p1.PrecursorMz, p2.PrecursorMz);
+                    return p1.PrecursorMz.CompareTo(p2.PrecursorMz);
                     // ReSharper restore PossibleNullReferenceException
                 }
             }
+
+            public override string ToString()
+            {
+                return $@"{PrecursorMz.RawValue} {NodePeptide}"; // For debug convenience, not user-facing
+            }
         }
     }
 }

pwiz_tools/Skyline/TestFunctional/ExportIsolationListTest.cs

@@ -23,11 +23,13 @@
 using System.Linq;
 using System.Text;
 using Microsoft.VisualStudio.TestTools.UnitTesting;
+using pwiz.Common.Chemistry;
 using pwiz.Skyline.Alerts;
 using pwiz.Skyline.FileUI;
 using pwiz.Skyline.Model;
 using pwiz.Skyline.Model.DocSettings;
 using pwiz.Skyline.Model.DocSettings.Extensions;
+using pwiz.Skyline.Model.Results;
 using pwiz.Skyline.Properties;
 using pwiz.Skyline.Util.Extensions;
 using pwiz.SkylineTestUtil;
@@ -151,6 +153,16 @@ protected override void DoTest()
             var ceFirst = AsSmallMoleculesNegative ? 20.3 : 20.4;
             var ceLast = AsSmallMoleculesNegative ? 19.1 : 19.2;
 
+            // Test an issue found in the PeptideFinder class with mixed polarity docs
+            if (SkylineWindow.Document.IsMixedPolarity())
+            {
+                var beyondMaxNegMz = (from precursor in SkylineWindow.Document.MoleculeTransitionGroups
+                    where precursor.PrecursorMz.IsNegative
+                    select precursor.PrecursorMz.RawValue).Min()-100.0;
+                var finder = new PeptideFinder(SkylineWindow.Document);
+                AssertEx.IsNull(finder.FindPeptide(new SignedMz(beyondMaxNegMz))); // This will throw a "polarity mismatch" exception if the issue is not fixed
+            }
+
             // Export Agilent unscheduled DDA list.
             ExportIsolationList(
                 "AgilentUnscheduledDda.csv",