title: System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia.
abstract: The relationship between cerebral ischemia and metabolic disorders is poorly understood, which is partly due to the lack of comparative fusing data for larger complete systems and to the complexity of metabolic cascade reactions. Based on the fusing maps of comprehensive serum metabolome, fatty acid and amino acid profiling, we identified 35 potential metabolic biomarkers for ischemic stroke. Our analyses revealed 8 significantly altered pathways by MetPA (Metabolomics Pathway Analysis, impact score >0.10) and 15 significantly rewired modules in a complex ischemic network using the Markov clustering (MCL) method; all of these pathways became more homologous as the number of overlapping nodes was increased. We then detected 24 extensive pathways based on the total modular nodes from the network analysis, 12 of which were new discovery pathways. We provided a new perspective from the viewpoint of abnormal metabolites for the overall study of ischemic stroke as well as a new method to simplify the network analysis by selecting the more closely connected edges and nodes to build a module map of stroke.
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.|Beijing Electric Power Hospital, Capital Medical University, Beijing, 100073, China.|Shanxi Buchang Pharmaceutical Co. Ltd, Xi'an, 712000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.|Jiaxing Traditional Chinese Medicine Affiliated Hospital of Zhejiang Chinese Medical University, Jiaxing, 314000, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, China.
authors.forename: Liangxiao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Yinying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanxi Buchang Pharmaceutical Co. Ltd, Xi'an, 712000, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Nan
authors.affiliation: Shanxi Buchang Pharmaceutical Co. Ltd, Xi'an, 712000, China.
authors.forename: Buchang
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers