Table 1.

Software tools developed for genome-scale metabolic reconstruction

Steps	Purpose of Tools	Implementation in the SEED	Database Contributions
ANNOTATION		The SEED already provides tools for annotation, based on similarity searching and context-based methods	The SEED already provides a database of high-quality genome annotations organized into subsystems (see [11])
SUB-ASSEMBLY AND SUB-NETWORK VERIFICATION	Curating associations between functional roles and reactions in a particular metabolic context	Reverse-engineering of published genome-scale metabolic models; analysis of gene-reaction associations in the KEGG database; integrated display of KEGG pathway maps in subsystems, highlighting functional roles and associated reactions	Associations between functional roles and KEGG reactions in subsystems
	Assembling and verifying the coherence of reaction subnetworks in subsystems	Petri net representation of KEGG reactions; encoded scenarios in subsystems; finding paths through reaction subnetworks from scenario inputs to scenario outputs	Reuseable coherent reaction subnetworks in subsystems
	Assembling and verifying the coherence of connected reaction subnetworks across subsystems	Connections between scenarios in different subsystems; finding paths through connected scenarios, from overall inputs to overall outputs	List of curated subsystems with coherent reaction subnetworks for functional variants that interconnect to cover central and intermediary metabolic pathways
ASSEMBLY AND NETWORK VERIFICATION	Assembling and verifying the coherence and completeness of an organism-specific reaction network	Identifying gaps in the reaction network, by cross-checking inputs and outputs for all paths through implemented scenarios, and checking for paths from minimal substrates to biomass compounds; creating files for FluxAnalyzer [36]	Organism-specific complete and coherent reaction networks for central and intermediary metabolism