Match the trees: Spectral trees of ionization fragments can identify metabolites

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  • Published: Jul 2, 2012
  • Author: Jon Evans
  • Channels: Laboratory Informatics
thumbnail image: Match the trees: Spectral trees of ionization fragments can identify metabolites

Ionization fragments

Match the trees: Spectral trees of ionization fragments can identify metabolites

Adapting a technique used to compare structural similarities between different molecules, Dutch biologists have come up with a novel method for identifying metabolites in tandem mass spectrometry (MS) data.

Conventionally, metabolites analysed by mass spectrometry are identified in one of two ways. Either a match for the generated mass spectra is found in a spectral database or the metabolite’s elemental composition is determined from the calculated masses of its component fragments. With tandem mass spectrometry, however, there is another way, which involves constructing mass spectral trees.

These spectral trees detail the various fragments produced from a single metabolite as it is repeatedly broken apart by hard ionization techniques such as electron impact ionization. The trees are made up of numerous nodes at various different levels, with each node representing a different fragment. The single top node represents the original metabolite; immediately below it is a layer of nodes representing the fragments produced when the metabolite is broken apart by hard ionization.

Below this is a layer representing the fragments produced when each of the initial fragments are broken apart by hard ionization, and so on. As each set of fragments is broken apart by ionization, another layer is added to the spectral tree.

 

Nodes and layers

Because different molecules fragment in different ways, the spectral tree for each metabolite is unique, in terms of the number of layers, the number of nodes in each of the layers and the measured masses of each of the nodes. In theory then, it should be possible to identify metabolites from their spectral trees. The question is how to do this in practice.

The only feasible way is to build up a database of spectral trees for known metabolites and then try to match the spectral trees for the metabolites in a sample against those in the database. This process can be made easier by first determining the elemental composition of some of the nodes from their masses, providing more information with which to make a match.

Last year, a team of Dutch biologists led by Theo Reijmers at the Netherlands Metabolomics Centre in Leiden produced a freely-available software tool called MEF (multistage elemental formula) for doing just that. In actual fact, MEF both automatically produces spectral trees from tandem mass spectrometry data and determines the elemental composition for at least some of the nodes in the tree.

 

Large-scale library

Now Reijmers and his team have gone a step further and developed a process for automatically comparing different trees to determine a match. Now, this is clearly no easy matter, as it requires comparing two graphical representations rather than just two numerical values. So they adapted a technique used to compare molecular structures, with the nodes taking the place of atoms and the links between the levels taking the place of bonds.

To test this adapted comparison technique, they took a random sample of 765 spectral trees from two spectral libraries of plant and human metabolites, and then compared them with all the trees in the libraries. Using the comparison technique, they could correctly match 722 of the trees, an accuracy of 94%; of those trees they failed to match correctly, most of them were wrongly matched to related isomers.

After demonstrating that the comparison technique broadly works, the next step is to develop a large-scale library of spectral trees to match against, allowing the technique to be used in general metabolomics studies. This is exactly what Reijimers and his team are now generating in the form of a web-based tool called MetiTree.

Related Links

Analytical Chemistry (Article in Press): "Metabolite identification using automated comparison of high-resolution multistage mass spectral trees"


Article by Jon Evans

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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