Metabolic Reconstruction
CarveMe (Recommended)
# Install CarveMe
pip install carveme
# Basic reconstruction from protein FASTA
carve genome.faa -o model.xml
# Specify output format
carve genome.faa -o model.xml --format sbml
carve genome.faa -o model.json --format json
# Gap-fill for specific media
carve genome.faa -o model.xml --gapfill M9
# Available media: M9, LB, M9[glc], M9[glyc], etc.
CarveMe Options
# Use diamond instead of blastp (faster)
carve genome.faa -o model.xml --diamond
# Specify organism type
carve genome.faa -o model.xml --grampos # Gram-positive
carve genome.faa -o model.xml --gramneg # Gram-negative (default)
# Initialize from template model
carve genome.faa -o model.xml --init M9
# Verbose output for debugging
carve genome.faa -o model.xml -v
gapseq (Alternative)
# Install gapseq
git clone https://github.com/jotech/gapseq
cd gapseq
./gapseq check # Check dependencies
# Full reconstruction workflow
./gapseq find -p all genome.fasta # Find metabolic pathways
./gapseq find -t all genome.fasta # Find transporters
./gapseq draft -r genome-all-Reactions.tbl \
-t genome-Transporters.tbl \
-p genome-all-Pathways.tbl \
-c genome.fasta
./gapseq fill -m genome-draft.RDS -c genome.fasta -n M9
Python API for CarveMe
import subprocess
def reconstruct_model(fasta_path, output_path, media='M9', grampos=False):
'''Run CarveMe reconstruction
Args:
fasta_path: Path to protein FASTA file
output_path: Output model file path (.xml or .json)
media: Gap-filling media (M9, LB, etc.)
grampos: True for Gram-positive organisms
Model size expectations:
- Bacteria: 1000-2500 reactions typical
- Fungi: 1500-3000 reactions
- Archaea: 800-1500 reactions
'''
cmd = ['carve', fasta_path, '-o', output_path, '--gapfill', media]
if grampos:
cmd.append('--grampos')
subprocess.run(cmd, check=True)
return output_path
Load and Inspect Draft Model
import cobra
model = cobra.io.read_sbml_model('model.xml')
print(f'Reactions: {len(model.reactions)}')
print(f'Metabolites: {len(model.metabolites)}')
print(f'Genes: {len(model.genes)}')
# Check if model can grow
solution = model.optimize()
print(f'Growth rate: {solution.objective_value:.4f}')
# List exchange reactions (available nutrients)
for rxn in model.exchanges[:10]:
print(f'{rxn.id}: {rxn.reaction}')
Quality Metrics
def assess_model_quality(model):
'''Basic quality assessment for draft model
Returns metrics to evaluate reconstruction quality.
'''
metrics = {
'reactions': len(model.reactions),
'metabolites': len(model.metabolites),
'genes': len(model.genes),
'gene_reaction_ratio': len(model.reactions) / max(1, len(model.genes))
}
# Count reaction types
metrics['exchanges'] = len(model.exchanges)
metrics['transport'] = len([r for r in model.reactions if 'transport' in r.name.lower()])
# Test growth
sol = model.optimize()
metrics['can_grow'] = sol.status == 'optimal' and sol.objective_value > 0.001
# Gene-reaction rules
metrics['orphan_reactions'] = len([r for r in model.reactions if not r.genes])
return metrics
Multiple Genome Reconstruction
import os
from pathlib import Path
def batch_reconstruction(fasta_dir, output_dir, media='M9'):
'''Reconstruct models for multiple genomes
Use for comparative genomics or community modeling.
'''
os.makedirs(output_dir, exist_ok=True)
for fasta in Path(fasta_dir).glob('*.faa'):
output = Path(output_dir) / f'{fasta.stem}.xml'
reconstruct_model(str(fasta), str(output), media=media)
print(f'Completed: {fasta.name}')
Community Model Construction
def merge_models(model_paths, community_name='community'):
'''Create community model from individual organisms
For microbiome FBA, need to create a shared compartment
for metabolite exchange between organisms.
'''
import cobra
models = [cobra.io.read_sbml_model(p) for p in model_paths]
# Add species prefix to all components
for i, model in enumerate(models):
species_id = f'sp{i+1}'
for rxn in model.reactions:
rxn.id = f'{species_id}_{rxn.id}'
for met in model.metabolites:
met.id = f'{species_id}_{met.id}'
for gene in model.genes:
gene.id = f'{species_id}_{gene.id}'
# Merge into community model
community = models[0].copy()
for model in models[1:]:
community.merge(model)
return community
Related Skills
- systems-biology/model-curation - Validate and curate draft models
- systems-biology/flux-balance-analysis - Analyze reconstructed models
- database-access/entrez-fetch - Download genome sequences
FridrichMethod