Overview of the Pathway Tools FBA Module

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

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

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

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

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