fba-simulator

Run Flux Balance Analysis (FBA) and related constraint-based simulations using COBRApy. Covers standard FBA, parsimonious FBA (pFBA), Flux Variability Analysis (FVA), loopless FBA, gene/reaction knockouts, and carbon source swapping. Outputs flux distributions and CSV files.

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Overview

The fba-simulator skill executes constraint-based metabolic simulations on a validated COBRApy model. FBA solves a linear program to find the flux distribution that maximizes (or minimizes) the objective function subject to stoichiometric and thermodynamic constraints.

This skill sits between model construction (gsmm-builder) and biological interpretation (flux-analyzer). All simulations are non-destructive: COBRApy context managers restore model state after each perturbation.

Workflow

Step 1 — Load Validated Model

import cobra
import cobra.io
import cobra.flux_analysis
import pandas as pd

model = cobra.io.load_json_model("my_model.json")
print(f"Model: {model.id}  Solver: {model.solver}")

Step 2 — Standard FBA

FBA maximizes the objective (typically biomass) subject to stoichiometric steady-state constraints: S·v = 0, lb ≤ v ≤ ub.

# Run FBA
solution = model.optimize()

print(f"Status          : {solution.status}")
print(f"Growth rate     : {solution.objective_value:.4f} h^-1")
print(f"Glucose uptake  : "
      f"{solution.fluxes['EX_glc__D_e']:.4f} mmol/gDW/h")
print(f"O2 uptake       : "
      f"{solution.fluxes.get('EX_o2_e', 0):.4f} mmol/gDW/h")
print(f"Acetate sec.    : "
      f"{solution.fluxes.get('EX_ac_e', 0):.4f} mmol/gDW/h")

# Save full flux distribution
solution.fluxes.to_csv("fba_fluxes.csv", header=["flux_mmol_gDW_h"])

Step 3 — Parsimonious FBA (pFBA)

pFBA first maximizes growth, then minimizes total absolute flux, producing the most "economical" solution consistent with maximum growth. This avoids biologically unrealistic high-flux split cycles.

pfba_solution = cobra.flux_analysis.pfba(model)

print(f"pFBA growth rate : {pfba_solution.objective_value:.4f} h^-1")
print(f"Total flux norm  : {pfba_solution.fluxes.abs().sum():.2f}")

pfba_solution.fluxes.to_csv("pfba_fluxes.csv", header=["flux_mmol_gDW_h"])

Step 4 — Flux Variability Analysis (FVA)

FVA computes the minimum and maximum flux each reaction can carry while maintaining at least fraction_of_optimum of the maximum growth rate. This reveals which fluxes are uniquely determined vs. flexible.

from cobra.flux_analysis import flux_variability_analysis

# FVA at 90% of maximum growth
fva_result = flux_variability_analysis(
    model,
    fraction_of_optimum=0.90,
    processes=4,          # parallel workers
)

# fva_result is a DataFrame with columns "minimum" and "maximum"
print(fva_result.head(10))

# Identify rigidly constrained reactions (min ≈ max)
TOLERANCE = 1e-6
rigid = fva_result[
    (fva_result["maximum"] - fva_result["minimum"]).abs() < TOLERANCE
]
print(f"\nRigid reactions (min=max): {len(rigid)}")

fva_result.to_csv("fva_result.csv")

Step 5 — Loopless FBA

Standard FBA may route flux through thermodynamically infeasible energy- generating cycles. Loopless FBA enforces thermodynamic feasibility.

loopless_sol = cobra.flux_analysis.loopless_solution(model)

print(f"Loopless growth  : {loopless_sol.objective_value:.4f} h^-1")
loopless_sol.fluxes.to_csv("loopless_fluxes.csv",
                            header=["flux_mmol_gDW_h"])

Step 6 — Gene Knockout Simulations

# Single gene knockout (context manager — model is restored after)
gene_id = "b0720"  # pgi in E. coli iJO1366

with model:
    model.genes.get_by_id(gene_id).knock_out()
    ko_solution = model.optimize()
    print(f"KO {gene_id} growth: {ko_solution.objective_value:.4f} h^-1")

# Batch single gene deletions
from cobra.flux_analysis import single_gene_deletion

deletion_results = single_gene_deletion(model)
# Returns DataFrame: index = frozenset({gene_id}), columns = [growth, status]
deletion_results.to_csv("gene_deletions.csv")

# Essential genes: growth < 5% of wild-type
wt_growth = model.optimize().objective_value
essential = deletion_results[
    deletion_results["growth"] < 0.05 * wt_growth
]
print(f"\nEssential genes: {len(essential)}")
print(essential.head())

Step 7 — Reaction Knockout Simulations

from cobra.flux_analysis import single_reaction_deletion

rxn_deletion_results = single_reaction_deletion(model)
rxn_deletion_results.to_csv("reaction_deletions.csv")

essential_rxns = rxn_deletion_results[
    rxn_deletion_results["growth"] < 0.05 * wt_growth
]
print(f"Essential reactions: {len(essential_rxns)}")

Step 8 — Carbon Source Swapping

CARBON_SOURCES = {
    "glucose":   ("EX_glc__D_e", -10.0),
    "fructose":  ("EX_fru_e",    -10.0),
    "acetate":   ("EX_ac_e",     -10.0),
    "glycerol":  ("EX_glyc_e",   -10.0),
    "succinate": ("EX_succ_e",   -10.0),
}

results = []

for carbon, (rxn_id, bound) in CARBON_SOURCES.items():
    with model:
        # Close all carbon exchange reactions first
        for r in model.exchanges:
            if r.lower_bound < 0 and r.id != "EX_o2_e":
                r.lower_bound = 0.0

        # Open the target carbon source
        if rxn_id in model.reactions:
            model.reactions.get_by_id(rxn_id).lower_bound = bound
            sol = model.optimize()
            results.append({
                "carbon_source": carbon,
                "growth_rate": sol.objective_value,
                "status": sol.status,
            })
        else:
            results.append({
                "carbon_source": carbon,
                "growth_rate": None,
                "status": "reaction_not_in_model",
            })

carbon_df = pd.DataFrame(results)
print(carbon_df)
carbon_df.to_csv("carbon_source_comparison.csv", index=False)

Step 9 — Aggregate and Save Results

summary = {
    "model_id": model.id,
    "wt_growth_fba": wt_growth,
    "wt_growth_pfba": pfba_solution.objective_value,
    "wt_growth_loopless": loopless_sol.objective_value,
    "n_essential_genes": len(essential),
    "n_essential_reactions": len(essential_rxns),
}

import json
with open("simulation_summary.json", "w") as f:
    json.dump(summary, f, indent=2)
print("Summary written to simulation_summary.json")

Key Conventions

Parameter	Recommended Value	Rationale
`fraction_of_optimum` (FVA)	0.9	10% growth slack — realistic variability
Essentiality threshold	growth < 5% WT	Standard in metabolic engineering
pFBA norm	L1 (sum abs fluxes)	COBRApy default; correlates with enzyme cost
Loopless FBA	Use for publication	Standard FBA may inflate central metabolism
`processes` (FVA)	4 or CPU count	Scales near-linearly; avoid >8 for small models

Output File Conventions

File	Content
`fba_fluxes.csv`	Standard FBA flux vector
`pfba_fluxes.csv`	pFBA flux vector (minimum total flux)
`fva_result.csv`	FVA minimum/maximum per reaction
`loopless_fluxes.csv`	Loopless-constrained flux vector
`gene_deletions.csv`	Growth rate for each single gene KO
`reaction_deletions.csv`	Growth rate for each single reaction KO
`carbon_source_comparison.csv`	Growth across different carbon sources
`simulation_summary.json`	Scalar summary of all simulation runs

Common Failure Modes

solution.status = "infeasible": medium is too restrictive or objective reaction bounds are wrong. Run gsmm-validator first.
Negative growth in pFBA: can occur if cobra.flux_analysis.pfba is called on an infeasible model — always check model.optimize() first.
FVA hangs: reduce processes or set loopless=False; large models (>10,000 reactions) may require HPC clusters.
Carbon source absent from model: check BIGG ID spelling carefully; use model.reactions.query("EX_") to list available exchanges.

Repository: aiming-lab/AutoResearchClaw
Path: external/agents/Biology-Agent/skills/fba-simulator/SKILL.md
Commit: e2e23c9

Last updated: 6 days ago
First committed: 3 months ago

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