1. Overview of the Pathway Tools FBA Module

2. The Pathway Tools Approach to FBA: FBA Model as a Database
Store and update metabolic model within Pathway Tools PGDB
Export to constraint solver for model execution
Fast generation of metabolic model from annotated genome
PGDB associates a wealth of information with FBA model
Chemical structures
The genome
Regulatory information
Literature citations
Evidence codes
Pathway definitions
Unique identifiers for each component of the model are used consistently across multiple PGDBs/models

3. The Pathway Tools Approach to FBA
Extensive query and visualization tools
Visualize individual metabolites, reactions, pathways
Metabolite page shows all reactions and transporters that act on that metabolite
Visualize reaction flux and omics data using Cellular Overview
Unique Cellular Overview generated for each PGDB
Debug/validate model using Pathway Tools
Dead-end metabolite analysis
Visual inspection on cellular overview
Reachability analysis
Store conditions of growth/non-growth in PGDB
Store knock-out phenotypes in PGDB

4. The Pathway Tools Approach to FBA
Multiple gap filling approach
Gap-fill reactions, reaction directions, nutrients, secretions, biomass metabolites
Combine automated and manual analysis for maximum accuracy

5. SRI FBA Results: E. coli Model
1330 reactions in the EcoCyc PGDB
370 reactions carry flux to produce 58 biomass metabolites
Model validated using the same knock-out data as used in Feist 2007
Our model: 86.1% accuracy on 873 genes
Feist et al 2007: 90.6% accuracy on same 873 genes

6. SRI FBA Results: Homo Sapiens Model
1720 reactions in PGDB
236 reactions carry flux to produce 51 biomass metabolites
~6 reactions suggested by gap filler were supported by literature research
Several suggested changes in reaction direction also supported by literature research