title: Prioritizing candidate disease metabolites based on global functional relationships between metabolites in the context of metabolic pathways.
abstract: Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Desi
authors.initials: D
authors.lastname: Shang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China; School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, P. R. China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Qianlan
authors.initials: Q
authors.lastname: Yao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Su
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Biomedical Engineering, Capital Medical University, No. 10 You An Men Wai Xi Tou Tiao, Beijing, P.R. China.
authors.forename: Dongguo
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012984:Software