Monday, 22 March 2010

Analysing Genome Scale Metabolic Models

David Fell

Create the soichiometry matrix for the complete metablism from the reaction lists from the annotated genomes. Then you can work out the null space matrix for the steady states (actually superset of steady states) which corresponds to the matrix which when multiplied by the stoichiometric matrix will give you the vertical matrix of the velocities (all zero at the steady states).
Calculate complete picture of fluxes at steady state by measuring some fluxes, and using these as multiplier of the  Flux analysis. Can simplify the matrix for those rows that are the same in the null space. Can also remove rows where they are all zero as these are dead enzymes in the steady state. Then you can add extra constraints - Pallson's Flux Balance Analysis.

When using a cost function it is called linear programming.

[Mathematically you could use Lagrangian Multipliers to test cost function and where it intersects with model space.]

  • Transport - need to find which molecules can be exchanged with the environment - genome analysis should reveal this.
  • Need to check for mass balance
  • Remove dead reactions
  • ScrumPy tests the stoichiometry matrix
  • Use PRIAM to improve annotation
  • Use simulated annealing to sample EC classification when it is ambiguous

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