From the two datasets, all molecules and reactions were recorded with their own identification numbers. Due to the use of different identifiers, to merge both datasets we used RDKit package to pairwise compare molecular canonical SMILES strings for all molecules, and reaction SMARTS for all reactions in both datasets. All KEGG molecules and reactions found in Reaxys were renamed with Reaxys identifier in the local datasets. An example of these molecules and reactions can be found in SI. The statistics of both datasets are shown in Figure . Data from KEGG is significantly more sparse compared with the dataset of reactions mined from Reaxys. Among KEGG data, a proportion of molecules and reactions overlap with the Reaxys data, since Reaxys includes mined reaction data regardless whether they are from organic synthetic or bio-synthetic sources. To compare the optimal reaction routes computed from candidate reactions from different sources, three local reactions pools were created: reactions from KEGG were labelled as a biological reactions pool (green + brown in Figure ), those from Reaxys and excluding the intersection between Reaxys and KEGG, were labeled as chemical reactions pool (pink), whilst the union of the two sets became the hybrid reactions pool (pink, green + brown). The visualisation of the hybrid reaction network in node and edge representation is shown in Figure .