Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Hu, Le-Le; Chen, Chen; Huang, Tao; Cai, Yu-Dong; Chou, Kuo-Chen

Recently, the systems biology methods based on protein-protein interactions have been widely applied for predicting protein attributes [15, 16, 17, 18, 19] . These algorithms suggest that interactive proteins are likely to share the common biological functions [16, 17, 18, 19] , also more likely tending to have the same biological function than non-interactive ones [20, 21] . Likewise, we can assume that the interactive compounds may tend to share the common biological functions. In this study, the chemical-chemical interactions were retrieved from STITCH [22] (Search tool for interactions of chemicals), where the interaction unit consists of two chemicals and their interaction weight. The interaction weight (confidence score) represents the probability that the interaction occurs between the two chemicals concerned. The interactive compounds can be classified into the following three categories: (I) ones that participate in the same reactions; (II) ones that share the similar structures or activities; (III) ones with the literature associations [22] . In a metabolism system, chemical reactions are organized into many metabolic pathways, thus the compounds involved in the same reactions are in the same metabolic pathways. Similar structures or activity means that they share the similar functions, and hence they are likely to be in the same metabolic pathways. The co-occurrence of two compounds in many literatures suggests some kinds of direct or indirect relationships, indicating they have the potential to be in the same metabolic pathways. Accordingly, it is rational to suppose that the interactive compounds tend to participate in the same metabolic pathways.