title: New strategy for drug discovery by large-scale association analysis of molecular networks of different species.
abstract: The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education; Pharmacology Department , School of Pharmacy, Shihezi University, Shihezi, Xinjiang, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Ziyin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education; Pharmacology Department , School of Pharmacy, Shihezi University, Shihezi, Xinjiang, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education; Pharmacology Department , School of Pharmacy, Shihezi University, Shihezi, Xinjiang, China.
authors.forename: Fukai
authors.initials: F
authors.lastname: Gong
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education; Pharmacology Department , School of Pharmacy, Shihezi University, Shihezi, Xinjiang, China.
authors.forename: Yuerong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Gao
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Xuetong
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.affiliation: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery; D005658:Fungi / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D001688:Biological Products; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D005978:Glutathione; D001205:Ascorbic Acid