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💬 9. General Discussion

  • What assumptions are made in genome-scale modelling approach?
    • What is mathematical optimization and how is it applied in FBA?
      • What are the variables? What is the S matrix?
      • What are the constraints?
      • What is the objective function?
  • What input data is required?
    • What are the pros and cons of using reference, MAGs, and SAGs for metabolic model reconstruction?
  • What type of data can be integrated, how, and what for?
    • E.g. transcriptomics, proteomics, metabolomics, etc.
  • How would you test the model predictions experimentally?
  • Can the model predict unexpected interactions?
  • Do you think this approach could be used in your project?
  • How can metaGEM be useful for large scale analysis of metagenomes?

🏁 Exercise 0: The data

  • Do you expect certain microbial communities to be cooperative or competitve? Why?
  • Rank the communities in the table above from most cooperative to most competitve and justify your answer.

🪚 Exercise 1: CarveMe model reconstruction

  • How does CarveMe generate metabolic models?
  • How does ORF-annotation of genome DNA influence model reconstruction?
  • What are the pros and cons of relying on the BiGG database for model reconstruction?
  • How does the choice of gap-filling media affect model reconstruction?
  • Why are there specialized model templates?

🧮 Exercise 2: CarveMe model visualization

  • Approximately how many genes do you expect to find in a typical prokaryotic genome? What percentage do you expect to be metabolism encoding?
  • Are the number of metabolites, reactions, and genes in your community's models comparable to other metabolic reconstructions?
  • Is there variation in the metabolism of conspecific models reconstructed from different metagenomes?

🕸️ Exercise 3: SMETANA detailed algorithm

  • How does the SMETANA detailed algorithm work at a high level?
  • What are the underlying assumptions?
  • What does each metric measure and how is it calculated?
    • SCS
    • MUS
    • MPS
    • SMETANA
  • What does a SMETANA score of 0 mean? What does a SMETANA score of 1 mean?
  • Why do we run multiple simulations and take averages of SMETANA scores? Why is it important to use the --zeros flag in this case?
  • How does choice of simulation media affect the SMETANA detailed algorithm output?
  • What does the --molweight flag do? How can it be useful?

📈 Exercise 4: SMETANA detailed visualization

  • Do the predictions make sense from a biological perspective?
  • How can these predictions be validated experimentally?
  • Look at the receiver species on your community's alluvial diagram, are they known to be auxotrophic for the metabolites we predicted them to uptake?
  • Look at the donor species on your community's alluvial diagram, are they known to be prototrophic for the metabolites we predicted them to donate?
  • Is there supporting literature for the predicted interactions in your community?
  • Can this approach be used for hypothesis generation in microbial ecology?

🌐 Exercise 5: SMETANA global algorithm

  • How does the SMETANA global algorithm work?
  • What are the underlying assumptions?
  • What does each metric measure and how is it calculated?
    • MIP
    • MRO
  • Does choice of media affect global score calculation?

⚖️ Exercise 6: SMETANA global visualization

  • How did your predicted competitiveness/cooperativeness rankings compare with the results from the plot above? Are you surprised by the results?
  • Why is there variation within communities, given that simulations were carried out using the same models?
  • Why might the simulations generated by some of our communities fall outside of the original publication's cooperation-coompetition plot (community size N=5)?

🎰 Exercise 7: CarveMe ensemble models (optional)

  • Why can there be differences between models generated from the same genome file?
  • How does the ensemble carving process work?
  • How can ensembles be useful for understanding network uncertainty?

❓ Exercise 8: CarveMe network uncertainity (optional)

  • Compare your community's plot with the one generated for CarveMe paper, is there more or less uncertainity?
  • What does it mean if the average/median Jaccard distance between models is 1 for a given ensemble?
  • What does it mean if the average/median Jaccard distance between models is 0 for a given ensemble?