Friday, January 28, 2011

1-28-2011 Computing Fragmentation Trees from Tandem Mass Spectrometry Data

Rasche, F, Svatoš, A, Maddula, RK, Böttcher, C, Böcker, S (2010). Computing Fragmentation Trees from Tandem Mass Spectrometry Data. Anal Chem, :np page given.

Goal: Annotate MS2 spectra of small molecules with chemical compositions.

Data: Orbi, QstAR, QTOF spectra of ~200 known compounds (<1KDa) with different CID energies
Build consensus spectra from different energies

Strategy
  1. Calculate chemical formula of parent mass from MS1 spectrum (given)
  2. Guild graph (DAG) of possible formulas to explain peaks
    • Node for each possible chem formula for a single peak (usually 3-4 nodes per peak)
    • Color nodes from the same peak with the same color
    • Edge between nodes if they could be generated by a plausible neutral loss
  3. Build tree from graph giving the most likely pattern of fragmentation to explain spectrum
    • Score nodes based on likelihood of that formula
    • Score edges according to known probabilities of various neutral losses
    • Want a 'colorful' graph, ie explains most peaks ("colors") in the spectrum, and few peaks have multiple formula associated
1-2 are solved heuristically.
Solve 3 formally:
Input: DAG + edge weights + set of colors
Output: Directed tree with maximal edge weight containing a unique set of colors
Solved by dynamic programming.

Conclusions
  • Fragment tree is alternate representation of spectra
  • Helps experts with manual peak annotation (somehow).
  • Better than existing greedy solution and other tools for predicting spectra from structure (Mass Frontier)
  • Could be used for comparing fragmentation trees to a library, but this isn't well developed.
  • No clear progress towards goal of determining structure from MS2

Critiques:
  •  Not very systematic in the analysis
  •  Poor paper organization
  •  Are fragment trees useful?
Speaker: Anand
Scribe: Spencer
Slides: here

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