In order to only use the relevant biological reactions for the shortest path calculation, a list of side metabolites was created (Table .1), for which the connected reactions were relabeled in the DSMN graph. This step allowed the algorithm to exclude the full list of metabolites deemed to be irrelevant to the actual biological process. Reactions between two side metabolites were labeled as ":SideInteractions". The original reactions' metadata properties were copied over to the new "Side interaction" relation, and the old reaction was removed to avoid redundancy in the edge data. The list with side metabolites was established with the following procedure: first, the highest in and out-degree and the number of occurrences of the metabolic reactions in different pathways were calculated. Second, the metabolites having a large in-degree, out-degree, occurring in multiple pathways, or a combination of these items were listed as potential side metabolites. Third, the biological background of these metabolites was investigated in the literature, after which the final list of side metabolites was created. Furthermore, all reactions connected to chemical elements, monoatomic cations, (halide) anions, and spurious nodes (e.g. DNA, RNA, electron) were relabeled in the network as side-metabolite, since these were considered irrelevant for the main biological reaction. The list of identifiers for these nodes was retrieved with the queries as depicted in Code Example 5 from the SPARQL endpoint of Wikidata (query.wikidata.org) on 2020-11-16.