Fig 4. Interest of heterogeneous methods in pathway completion and filling thanks to tracking of process metadata.

Completion of the 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I and the tetrahydrofolate biosynthesis pathways in E. siliculosus via the combination of annotation (yellow), orthology (green) and gap-filling (blue). The dihydrofolate compound with the dotted line is an instance of the dihydrofolate-glu-n class, following MetaCyc classes ontology structure. The class compound is the original reactant of the dihydrofolatereduct-rxn reaction retrieved with annotation, whereas the previous reaction of the pathway (dihydrofolatesynth-rxn) produces the instance dihydrofolate. Hence the gap-filling step that, using an extended version of MetaCyc, selects an instantiated version of dihydrofolatesynth-rxn that consumes the instance dihydrofolate.