Fig. 2

A simplified example showing the three phases of the algorithm. In this example, the user has specified a single condition, transcription factor TF0, and a single effect, metabolite M0, both colored yellow throughout. a A simple metabolic and regulatory network consisting of five enzyme-catalyzed reactions and three transcription factors. E1 catalyzes the conversion of metabolite M0 to metabolite M1. Transcription factor TF0 inhibits expression of transcription factor TF1, and activates expression of enzyme E5. b The graph G1 generated during Phase 1. For this simplified example, assume all edge weights are 1. In actual operation, the edge weights would be determined by the formulae in Table 1. c In Phase 2, we search for paths connecting M0 and TF0. The shortest path is shown in dark green, but the paths shown in light green are only slightly longer, so all three are kept. The filtered graph G2 contains only the colored nodes and edges. d In Phase 3, considering only the edges associated with reactions (colored orange), we divide the graph into connected components, and create two temporary pathways, one consisting of reactions R1,R2 and R3, and the other consisting of just R5. The remainder of the graph (colored blue) is also divided into connected components. e Each of the components is laid out individually. We use Pathway Tools’ automated pathway layout algorithms for the temporary pathways, suppressing display of any enzymes or side metabolites that are not part of G2. f The individual components are reassembled and appropriate node and edge styles assigned to form the Explanation Graph G3