Abstract
Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.
Highlights
Metabolism refers to a collection of chemical reactions in vivo, which keep an unceasing supply of matter and energy for living organisms to maintain life [1]
We proposed a multi-target model based on chemical-chemical interactions for predicting the metabolic pathways where compounds participate in
KEGG [14] (Kyoto Encyclopedia of Genes and Genomes) compound [ftp://ftp.genome.jp/pub/kegg/release/archive/ kegg/42/ligand.tar.gz]. These compounds were mapped to the following 11 major metabolic pathway classes that are strongly associated with the biological functions of compounds: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism
Summary
Metabolism refers to a collection of chemical reactions in vivo, which keep an unceasing supply of matter and energy for living organisms to maintain life (e.g., growth and reproduction) [1]. Diabetes mellitus is a metabolic disease caused by insufficient or inefficient insulin secretary response and elevated blood glucose level [3]. Compounds such as sulfonylureas [4], acarbose [5], biguanides, thiazolidinediones [5], and sitagliptin [3] have been used as effective drugs for diabetic therapy. It is essential to annotate the bioactivities of compounds, which will benefit drug design and disease treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
