Monday, 29 June 2009

Network Based Prediction of Metabolic Enzyme Sub-cellular Localisation

Shira Mintz-Oron***
Clear and easy to understand talk but the method seems very complex, it is necessary to go to the flux level?

GFP and microscopy are the experimental techniques but they are costly and difficult in higher eukaryotes.

Localisation is by motifs, composition, homology etc.
Here predict localisation based on metabolic networks.
Prior knowledge of the localisation of a subset of the network is needed, want to minimise the number of membrane transport reactions (thermodyamic cost).
Use constraint based modelling to predict the flux rate at a steady state, predict the flux rates under constraints of mass balance, thermodynamic constraints and enzymatic capacity (rate bounds). Maximise biomass production.

  1. Divide the data into the localised and the unlocalised (unknowns) enzymes.
  2. Put all the enzymes into all compartments - build all the transport reactions limit enzyme activity for known localised reactions to the compartments in which they are known to be active.
  3. Give a unit penalty for transport reactions - want a low penalty so that some transport is allowed.
Fuzzy classification so gets scores for more than one compartment and so this means that a distribution across multiple compartments is possible.

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