title: Immune response- and viral control-related pathways in the progression of chronic hepatitis B.
abstract: BACKGROUND
  Chronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases.
  
  
  OBJECTIVE
  This study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction.
  
  
  METHODS
  In this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway.
  
  
  RESULTS
  We constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state.
  
  
  CONCLUSIONS
  By pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.
authors.affiliation: Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zou
authors.affiliation: Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Ren-Liang
authors.initials: RL
authors.lastname: Qu
authors.affiliation: Department of Hepatobiliary Internal Medicine, Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai 264001, China. Electronic address: 15564536548@163.com.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Xu
mesh_terms: D019295:Computational Biology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans
keywords: Chronic hepatitis B; Differential co-expression network; Host response; Sub-network