Afternoon tutorial

The bigg_e_coli_core Escherichia coli K12 model is a simplified metabolic network model and is (almost) identical to the model published as supporting material in Orth et al. (2010). The following exercises are inspired by this document.

Warming up

  • Reset your session
  • Pick the bigg_e_coli_core E. coli model from the model and pathway repository

Create a modified model

The idea is to create a new model for the anaerobic growth of E. coli K12:
  • Determine the Reac ID of the boundary reaction for O2
  • Export the bigg_e_coli_core model as an Excel spreadsheet (or in any other format but Excel is rather convenient)
  • In the enzymes sheet, find the row with the correct Reac ID, and set the flux boundaries to [0;0] thus preventing O2 from entering or leaving the system
  • Save the model in the corresponding format on the user side (with a new name).
  • Upload the new model using an informative model identifier, e.g. anaerobic_textbook
  • Using the reac_list view, inspect the original and modified model. Do the two models differ where they are expected to differ?

Flux balance analysis (FBA)

Run FBA on both models.
  • Can you identify any changes in the external flux distributions between the two models?
  • Can you establish the overall growth stoichiometry for both models. Are they compatible with E. coli K12 biology?
  • Can you identify any internal reactions which change direction?
  • What would happen to the FBA solution if all reactions are unconstrained?

Reaction knockout

Run the reaction knockout analysis on both the aerobic and anaerobic models.
  • How many reactions are essential in each model?
  • Are there reactions that are essential in one growth condition and not in the other one?
  • Are there reactions with beneficial knockout? If so, can you explain why?

A more realistic model

Add the model iAF1260 to your workspace and compare it to the bigg_e_coli_core model with respect to (1) biomass flux, (2) dead-end reactions, (3) correlation groups.

Expanding the bigg_e_coli_core model

Insert one or two additional amino acids in the bigg_e_coli_core model. Don't forget to improve the biomass reaction?