Automated Metabolic Network Reconstruction using Orthology

We used three manually curated metabolic networks, that of Escherichia coli K12 [22 (link)], Lactobacillus plantarum WCFS1 [B. Teusink et al., manuscript in preparation, see also [17]] and Bacillus subtilis subsp. subtilis str. 168 [33 ], as a source to predict automatically a metabolic network for Lactococcus lactis IL1403. The developed method is called AUTOGRAPH (AUtomatic Transfer by Orthology of Gene Reaction Associations for Pathway Heuristics, see Figure 1) and is outlined in detail below. The curated networks were initially constructed with Genomatica's Simpheny™ software for constraint-based modeling purposes, and were retrieved as flat-files containing gene-protein-reaction associations [42 ].
A reference metabolic network of L. lactis IL1403 has been used to evaluate our method (discussed below). This network was also constructed for constraint-based modeling purposes and was retrieved from the authors as a flat-file, containing gene-reaction associations. Throughout the article we will refer to this published reference network as the Oliveira network [31 (link)].
To compare the automatic reconstruction of L. lactis IL1403 metabolic network by Pathologic with that of our method, we used the Genbank NCBI annotation file of L. lactis IL1403 as input for the Pathologic software [27 (link),43 ]. In addition, the same Genbank file together with two manually curated networks from the BioCyc collection (i.e. EcoCyc [16 (link)] and LacplantCyc [17 (link)]) were used as inputs for our method (discussed below).