I upgraded the original ffly4 workspace, then set it to accept samples without MS2 IDs and left it recalculating results. I did so with two instances of Topograph running. When I returned a couple hours later, I saw a dialog box telling me that Topograph had stopped working and asking me if I wanted to check for a solution or just close the program. The detailed error message from that dialog box is pasted below, as is an error message from Topograph itself.

Note that I started the recalculation right after upgrading the workspace. Topograph displayed the "changed" message in the top bar of the program window, but when I tried to save, it didn't do anything in response.

*
Description:
  Stopped working

Problem signature:
  Problem Event Name:    CLR20r3
  Problem Signature 01:    topograph.exe
  Problem Signature 02:    1.0.0.0
  Problem Signature 03:    4ed8682f
  Problem Signature 04:    mscorlib
  Problem Signature 05:    2.0.0.0
  Problem Signature 06:    4d4cc8cb
  Problem Signature 07:    1ec
  Problem Signature 08:    0
  Problem Signature 09:    System.OutOfMemoryException
  OS Version:    6.1.7600.2.0.0.768.3
  Locale ID:    1033


System.OutOfMemoryException: Exception of type 'System.OutOfMemoryException' was thrown.
   at MathNet.Numerics.LinearAlgebra.Matrix.CreateMatrixData(Int32 m, Int32 n)
   at MathNet.Numerics.LinearAlgebra.Matrix.Multiply(Matrix B)
   at pwiz.Topograph.Enrichment.TurnoverCalculator.FindBestCombination(Vector targetVector, Vector[] candidateVectors)
   at pwiz.Topograph.Enrichment.TurnoverCalculator.FindBestCombination(Vector targetVector, Vector[] candidateVectors, Boolean errOnSideOfLowerAbundance)
   at pwiz.Topograph.Enrichment.TurnoverCalculator.FindBestCombinationFilterNegatives(Vector observedIntensities, IList`1 candidates)
   at pwiz.Topograph.Enrichment.TurnoverCalculator.FindBestCombinationFilterNegatives(Vector observedIntensities, IList`1 candidates, Func`2 excludeFunc)
   at pwiz.Topograph.Enrichment.TurnoverCalculator.GetTracerAmounts(IList`1 observedIntensities, Double& score, IDictionary`2& predictedIntensities, IList`1 tracerFormulas, IList`1 theoreticalIntensities)
   at pwiz.Topograph.Model.TracerChromatograms..ctor(Chromatograms chromatograms, Boolean smoothed)
   at pwiz.Topograph.Model.PeptideFileAnalysis.GetTracerChromatograms(Boolean smoothed)
   at pwiz.Topograph.Model.Peaks.GetTracerChromatograms()
   at pwiz.Topograph.Model.Peaks.FindBestPeak(IEnumerable`1 otherPeaks)
   at pwiz.Topograph.Model.Peaks.FindPeak(IEnumerable`1 otherPeaks)

Not really maintaining Topograph any longer.