Metabolism

CORNETO brings constraint-based metabolic modeling into the same optimization framework used for other network-inference problems. It interoperates with COBRApy models and supports standard flux balance analysis while exposing the formulation for custom constraints, coupled conditions, shared sparsity, and omics integration.

Start with standard FBA and model interoperability, continue with multi-condition FBA and shared reaction selection, and then integrate expression evidence first in one condition and later across several conditions.

• Flux balance analysis
  • From COBRApy to CORNETO
    • Solve the COBRApy model
    • Convert the model and solve with CORNETO
  • Extend the optimization problem
  • Solve multiple media conditions
  • Sparse FBA
• Multi-condition FBA
  • Independent and coupled formulations
  • Why is this different from pairwise comparisons?
  • Relation to COBRApy
  • Example: shared and context-specific metabolism
  • Define the metabolic conditions
  • Establish each condition’s growth capacity
  • Require growth and favor a compact reaction union
  • What happens in separate two-condition analyses?
  • Solve all conditions jointly
    • Shared and context-specific reaction usage
    • Biological interpretation
    • Visualize the joint metabolic program
    • Compare the selected unions
  • Interpretation and limitations
• Integrating gene expression into metabolic models
  • One established approach: iMAT
  • From genes to reaction evidence
  • Relationship to COBRApy
  • Example: selecting an anaerobic fermentation program
    • Check that the required phenotype is feasible
    • Define a qualitative expression profile
    • An expression-free reference
    • Build and solve iMAT
    • Did the inferred state agree with expression?
    • Compare the selected fermentation routes
    • Visualize the contextualized metabolic network
  • Advanced: compute and supply reaction scores directly
  • Interpretation and limitations
• Multi-condition gene expression integration
  • What changes in the multi-condition formulation?
  • Example: aerobic respiration and anaerobic fermentation
    • Define condition-specific reaction evidence
    • Define the media and required phenotypes
  • Balance expression evidence across conditions
  • Independent iMAT as a reference
  • Solve both expression contexts jointly
    • Inspect reaction-level expression agreement
    • What did joint inference change?
  • Shared and condition-specific metabolism
    • Biological interpretation
    • Visualize the jointly inferred network
  • Interpretation and limitations