The bigg_e_coli_core model is a very simplified metabolic network model of Escherichia coli K12.
This toy model is almost identical to the one in
et al. (2010). Note that we can only recommend reading this excellent primer as a complement to our hands-on tutorial.
- Reset your session (there is nothing to do if it is your first visit to the site, alternatively "Reset session" can be found in the menu on the left)
- Pick the bigg_e_coli_core E. coli model from the model and pathway repository:
- click on the "Pick from repository" menu on the left
- select the model checkbox (writing "coli" in the search box should help you find the model)
- press the "Add to my Selection" button
- You have now the model uploaded in your sandbox (you can always return to it by using the "Summary" menu).
- MetaNetX.org treats each model (i.e., metabolic network or pathway) as an being constituted of different entities:
chemical compounds (chem)
subcellular compartments (comp)
species (spec): chemical compounds that are assigned to a subcellular compartment
metabolic reactions (reac): reactions that transform species into another
genes or peptides (pept): the two are currently not distinguished, which make more
"enzymes" (enzy): sets of peptides (or genes) linked to a reaction with information on bounds (maximal and minimal bounds) defining the directionality such that the maximum flux can be carried by this reaction with these enzymes
- Depending on the studied model (GEM or pathway), it may contain biomass production reaction(s) (identified by the identifier "BIOMASS" in the corresponding reaction equation), or uptake or secretion reactions (external/boundary reactions; identified by chemical species associated with the artificial "BOUNDARY" compartment).
- What are the total number of reactions, chemical compounds, and compartments in the model?
- This is automatically displayed in the sandbox: #reac=97, #chem=56 and #comp=3. Indeed, a very small model.
- What is the total number of external (or boundary) reactions?
- What are the total numbers of reversible or irreversible reactions?
- How many reactions occur in a single compartment only? What kind of reactions are the remaining reactions? What is their total number?
- The answers can be found in the BC (Basic Classification) analysis summary, found on the right of the sandbox
- Restrict the display to external reactions in the reac_list view
by typing BOUNDARY in the search field. What can you tell about the growth conditions, i.e. about the "growth medium" of E. coli K12 as modelled by bigg_e_coli_core? What does it mean that some external reactions are unconstrained/unidirectional/bidirectional?
- D-glucose is the sole carbon source that can be consumed with an absolute uptake rate of 10.0
(the negative sign indicates that this boundary reaction proceeds from right to left).
- Phosphate, ammonium, water, proton, oxygen, and carbon dioxide are available in excess.
They can be "freely" exchanged (imported or exported) at the system boundary, as no particular flux constraints are placed on these reactions.
- The remaining organic compounds (e.g. acetate) occurring in the external compartment can only be exported and thus correspond to possibly secreted metabolites. In other words, they are not present in the medium defined by default.
The bigg_e_coli_core model is a (very) simplified metabolic network.
- What can you tell about its growth reaction? Is it biologically relevant?
- What can you tell about the metabolism of sulfur?
- Identify the growth reaction in the reac_list view by, for example, typing BIOMASS in the search field... What a simplified growth reaction!! Only two amino acids are required for growth: glutamate and glutamine.
- There are no sulfur compounds in the set of boundary reactions - the sulfur metabolism is completely ignored although sulfur atoms occur in some metabolites, e.g. CoA!
Run the GCR (groups of coupled reactions) and FBA (flux balance analysis) on bigg_e_coli_core model.
Run the GCR and BLO analysis methods. Their outcome strongly depends on the network topology and are extremely helpful to optimize a model
- Does the model grow? What if the flux of biomass production?
Run the RKO and PKO analysis methods. Their predictions might be compared with independently acquired experimental results (e.g. gene essentiality) and used to validate the model (this is not directly feasible in web interface, unfortunately).
- Can you identify any reaction correlation groups? How do they relate to the flux distribution?
- Can you identify any reaction correlation groups that cannot carry a flux in steady state? If so, why?
The idea is to create a new model for the anaerobic growth of E. coli K12:
- Reset the session and re-import the bigg_e_coli_core model, such as all previously made analyses will be erased (thus simplifying the display)
- Use the "Show/hide columns" button on the right of the reac_list to select "Reac ID:" as a column to be displayed
- Determine the Reac ID of the boundary reaction of O2 (Answer: mnxr102090c2b)
- Export the bigg_e_coli_core model in SBML3 format (Excel might be more convenient for performing a quick change, but the Excel format provided by MetaNetX is not compatible with any other software)
- Find the line containing 'mnxr102090c2b'. It is part of an XML block containing something like: