Identification of reaction organization patterns that naturally cluster enzymatic transformations

BACKGROUND: Metabolic reactions are chemical transformations commonly catalyzed by enzymes. In recent years, the explosion of genomic data and individual experimental characterizations have contributed to the construction of databases and methodologies for the analysis of metabolic networks. Some methodologies based on graph theory organize compound networks into metabolic functional categories without preserving biochemical pathways. Other methods based on chemical group exchange and atom flow trace the conversion of substrates into products in detail, which is useful for inferring metabolic pathways. METHODS: Here, we present a novel rule-based approach incorporating both methods that decomposes each reaction into architectures of compound pairs and loner compounds that can be organized into tree structures. We compared the tree structure-compound pairs to those reported in the KEGG-RPAIR dataset and obtained a match precision of 81%. The generated tree structures naturally clustered all reactions into general reaction patterns of compounds with similar chemical transformations. The match precision of each cluster was calculated and used to suggest reactant-pairs for which manual curation can be avoided because this is the main goal of the method. We evaluated catalytic processes in the clusters based on Enzyme Commission categories that revealed preferential use of enzyme classes. CONCLUSIONS: We demonstrate that the application of simple rules can enable the identification of reaction patterns reflecting metabolic reactions that transform substrates into products and the types of catalysis involved in these transformations. Our rule-based approach can be incorporated as the input in pathfinders or as a tool for the construction of reaction classifiers, indicating its usefulness for predicting enzyme catalysis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12918-018-0583-9) contains supplementary material, which is available to authorized users.