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

Initialization:
  • 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?