text: A reconstruction is built by compiling data from the resources above.  Database tools such as KEGG and BioCyc can be used in conjunction with each other to find all the metabolic genes in the organism of interest.  These genes will be compared to closely related organisms that have already developed reconstructions to find homologous genes and reactions. These homologous genes and reactions are carried over from the known reconstructions to form the draft reconstruction of the organism of interest. Tools such as ERGO, Pathway Tools and Model SEED can compile data into pathways to form a network of metabolic and non-metabolic pathways. These networks are then verified and refined before being made into a mathematical simulation.
  The predictive aspect of a metabolic reconstruction hinges on the ability to predict the biochemical reaction catalyzed by a protein using that protein's amino acid sequence as an input, and to infer the structure of a metabolic network based on the predicted set of reactions. A network of enzymes and metabolites is drafted to relate sequences and function.  When an uncharacterized protein is found in the genome, its amino acid sequence is first compared to those of previously characterized proteins to search for homology.  When a homologous protein is found, the proteins are considered to have a common ancestor and their functions are inferred as being similar.  However, the quality of a reconstruction model is dependent on its ability to accurately infer phenotype directly from sequence, so this rough estimation of protein function will not be sufficient.  A number of algorithms and bioinformatics resources have been developed for refinement of sequence homology-based assignments of protein functions:
  * [http://inparanoid.sbc.su.se/cgi-bin/index.cgi InParanoid]:  Identifies eukaryotic orthologs by looking only at in-paralogs.
  * [https://www.ncbi.nlm.nih.gov/cdd CDD]:  Resource for the annotation of functional units in proteins. Its collection of domain models utilizes 3D structure to provide insights into sequence/structure/function relationships.
  * [http://www.ebi.ac.uk/interpro/ InterPro]:  Provides functional analysis of proteins by classifying them into families and predicting domains and important sites.
  * [http://string.embl.de/ STRING]:  Database of known and predicted protein interactions.
  Once proteins have been established, more information about the enzyme structure, reactions catalyzed, substrates and products, mechanisms, and more can be acquired from databases such as [http://www.kegg.jp/ KEGG], [http://www.metacyc.org/ MetaCyc] and [http://www.chem.qmul.ac.uk/iubmb/enzyme/ NC-IUBMB].  Accurate metabolic reconstructions require additional information about the reversibility and preferred physiological direction of an enzyme-catalyzed reaction which can come from databases such as [https://web.archive.org/web/20150506193454/http://www.brenda-enzymes.org/ BRENDA] or [http://www.metacyc.org/ MetaCyc] database.