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Model Curation - Usage Guide

Overview

Curation turns a draft genome-scale model into a trustworthy one, and it splits into two axes that must not be confused. The first is consistency and annotation - mass and charge balance, no stoichiometric leaks, SBO terms, SBML/FBC conformance - which memote scores. The second is predictive validity - does the model reproduce measured growth, carbon-source usage, and gene essentiality - which memote does not score. A model can reach a 90% memote score and still mispredict every knockout, so a high score means well-formed and well-annotated, never "biologically correct." The single most dangerous defect a good score can hide is an energy-generating cycle that makes ATP from nothing; it passes mass balance, inflates growth, and invalidates flux predictions, so test for it explicitly. Gap-filling forces growth on a chosen medium and its added reactions are the least-evidenced part of the model.

Prerequisites

pip install memote cobra
# A universal reaction database (e.g. a BiGG universal model SBML) is needed for gap-filling.

Inputs: a genome-scale model in SBML (a draft from metabolic-reconstruction, or a published model), and for gap-filling a universal reaction database in the same namespace. For validation, measured growth/essentiality data on a defined medium.

Quick Start

Tell your AI agent: - "Run memote on my model and tell me which tests fail, not just the score" - "Check whether my model can make ATP from nothing" - "Gap-fill my model to grow on M9, and list what was added so I can flag it" - "Find unbalanced reactions and dead-end metabolites" - "My model scores 85% but mispredicts knockouts - what should I actually validate?"

Example Prompts

Interpreting a Score

"Run memote on my model, report the total score, and then explain what the score does and does not tell me about whether the model predicts biology."

Energy-Generating Cycles

"Close all exchanges and check whether my model can still produce ATP; if it can, help me find and constrain the reactions forming the erroneous energy-generating cycle."

Gap-Filling

"My draft cannot grow on M9 glucose. Gap-fill it from the BiGG universal model, show me the alternative gap-fill sets, and mark the added reactions as low-confidence."

Validation

"My model has a high memote score. Compare its predicted gene essentiality to the Keio set on M9 and its carbon-source usage to Biolog data, and report where it fails."

What the Agent Will Do

  1. Load the model and run memote (memote run / report snapshot), reading which tests fail, not just the total.
  2. Run the energy-generating-cycle test (max ATP with all uptake closed must be ~0) and constrain directionality if it fails.
  3. Find mass/charge-unbalanced reactions (skip exchange/sink/demand) and fix protons/charge first.
  4. Locate dead-end metabolites and decide whether to add a reaction or fix stoichiometry.
  5. Gap-fill deliberately toward the objective on a stated medium, recording and flagging added reactions.
  6. Validate predictive quality against measured growth/essentiality on the matched medium - the step memote does not perform.

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