title: A Two-layer Model to Identify Hepatitis B Virus Related Chronic Hepatitis and Liver Cirrhosis Based on Plasma microRNA Biomarkers.
abstract: BACKGROUND
  Accurate diagnosis of chronic Hepatitis B virus (HBV) infection related diseases is crucial to guide the therapy and to understand the mechanisms of disease progression. Plasma microRNAs, as stable biomarkers, have drawn significant attentions for distinguishing HBVrelated diseases.
  
  
  METHODS
  In this study, a new HBV-related disease identification method based on a two-layer logistic regression model was presented. A total of nine effective plasma microRNA biomarkers were selected through sample collection, data processing, model selection, feature selection and model optimization to distinguish HBV-related chronic hepatitis and cirrhosis samples as well as healthy controls. The first layer utilized three microRNAs to distinguish HBV-related disease samples from healthy controls. Then the second layer divided the HBV-related disease samples into cirrhosis and chronic hepatitis samples by using eight microRNAs.
  
  
  RESULTS
  Test on two independent cohorts showed high accuracy and robustness of our model. Functional analysis of the selected microRNAs and their target genes confirmed that they were significantly associated with HBV-related diseases and related functional pathways.
  
  
  CONCLUSIONS
  Compared with previous models, the two-layer model was more consistent with the underlying pathological progress of HBV related diseases from health to chronic hepatitis and further to liver cirrhosis. It could also take the results of other diagnostic tests into account, which could be useful in both physical examination and disease diagnosis.
authors.affiliation: School of Biological Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Hou
authors.affiliation: Key Lab of Computational Biology CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing QuantoBio Biotechnology Co. Ltd, No.1, Disheng East Road, Beijing Economic-Technological Development Area, Daxing District, Beijing 100176, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Jin
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing QuantoBio Biotechnology Co. Ltd, No.1, Disheng East Road, Beijing Economic-Technological Development Area, Daxing District, Beijing 100176, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Sun
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, No.8, Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, No.8, Xitoutiao, Youanmenwai, Fengtai District, Beijing 100069, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing QuantoBio Biotechnology Co. Ltd, No.1, Disheng East Road, Beijing Economic-Technological Development Area, Daxing District, Beijing 100176, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Beijing QuantoBio Biotechnology Co. Ltd, No.1, Disheng East Road, Beijing Economic-Technological Development Area, Daxing District, Beijing 100176, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Biological Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000821:virology*; D016015:Logistic Models; D035683:MicroRNAs / Q000097:blood*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: HBV; Two-layer model; chronic hepatitis; cirrhosis; logistic regression