title: Investigation of the roles of trace elements during hepatitis C virus infection using protein-protein interactions and a shortest path algorithm.
abstract: Hepatitis is a type of infectious disease that induces inflammation of the liver without pinpointing a particular pathogen or pathogenesis. Type C hepatitis, as a type of hepatitis, has been reported to induce cirrhosis and hepatocellular carcinoma within a very short amount of time. It is a great threat to human health. Some studies have revealed that trace elements are associated with infection with and immune rejection against hepatitis C virus (HCV). However, the mechanism underlying this phenomenon is still unclear.
  
  
  
  In this study, we aimed to expand our knowledge of this phenomenon by designing a computational method to identify genes that may be related to both HCV and trace element metabolic processes. The searching procedure included three stages. First, a shortest path algorithm was applied to a large network, constructed by protein-protein interactions, to identify potential genes of interest. Second, a permutation test was executed to exclude false discoveries. Finally, some rules based on the betweenness and associations between candidate genes and HCV and trace elements were built to select core genes among the remaining genes.
  
  
  
  12 lists of genes, corresponding to 12 types of trace elements, were obtained. These genes are deemed to be associated with HCV infection and trace elements metabolism.
  
  
  
  The analyses indicate that some genes may be related to both HCV and trace element metabolic processes, further confirming the associations between HCV and trace elements. The method was further tested on another set of HCV genes, the results indicate that this method is quite robustness.
  
  
  
  The newly found genes may partially reveal unknown mechanisms between HCV infection and trace element metabolism. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai 200444, People's Republic of China.
authors.forename: LiuCun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai 200444, People's Republic of China.
authors.forename: XiJia
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, People's Republic of China.
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai 200444, People's Republic of China. Electronic address: cai_yud@126.com.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Cai
mesh_terms: D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps / Q000235:genetics*; D014131:Trace Elements / Q000009:adverse effects* / Q000378:metabolism*
chemical_list: D014131:Trace Elements
keywords: HCV; Permutation test; Protein-protein interaction; Shortest path algorithm; Trace element