A Data-Driven Approach for Identifying Medicinal Combinations of Natural Products

Combinations of natural products have been used as important sources of disease treatments. Existing databases contain information about prescriptions, herbs, and compounds and their relationships with phenotypes, but they do not have information on the use of combinations of natural product compounds. In this paper, we identified large-scale associations between natural product combinations and phenotypes by applying an association rule mining technique to integrated information on herbal medicine, combination drugs, functional foods, molecular compounds, and target genes. The rationale behind this approach is that natural products commonly found in medicinal multicomponent mixtures have statistically significant associations with the therapeutic effects of the multicomponent mixtures. Based on a molecular network analysis and an external literature validation, we show that the inferred associations are valuable information for identifying medicinal combinations of natural products since they have statistically significant closeness proximity in the molecular layer and have much experimental evidence. All results are available through the workbench site at http://biosoft.kaist.ac.kr/coconut to facilitate the investigation of the medicinal use of natural products and their combinations.