Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts.

Journal: Scientific reports
Published Date:

Abstract

Chronic infection with Hepatitis B virus (HBV) is a major risk factor for the development of advanced liver disease including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The relative contribution of virological factors to disease progression has not been fully defined and tools aiding the deconvolution of complex patient virus profiles is an unmet clinical need. Variable viral mutant signatures develop within individual patients due to the low-fidelity replication of the viral polymerase creating 'quasispecies' populations. Here we present the first comprehensive survey of the diversity of HBV quasispecies through ultra-deep sequencing of the complete HBV genome across two distinct European and Asian patient populations. Seroconversion to the HBV e antigen (HBeAg) represents a critical clinical waymark in infected individuals. Using a machine learning approach, a model was developed to determine the viral variants that accurately classify HBeAg status. Serial surveys of patient quasispecies populations and advanced analytics will facilitate clinical decision support for chronic HBV infection and direct therapeutic strategies through improved patient stratification.

Authors

  • Alan J Mueller-Breckenridge
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. alan_james.mueller-breckenridge@roche.com.
  • Fernando Garcia-Alcalde
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
  • Steffen Wildum
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
  • Saskia L Smits
    Department of Viroscience, Erasmus Medical Center, Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
  • Robert A de Man
    Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Margo J H van Campenhout
    Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Willem P Brouwer
    Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Jianjun Niu
    Zhongshan Hospital Xiamen University, 205 Hubin S Rd, Siming Qu, Xiamen, 361000, Fujian, China.
  • John A T Young
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
  • Isabel Najera
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
  • Lina Zhu
    Department of Obstetrics and Gynecology, Affiliated Huaihai Hospital of Xuzhou Medical University 226 Tongshan Road, Xuzhou 221004, Jiangsu, China.
  • Daitze Wu
    Roche Innovation Centre Shanghai, Roche R&D Centre (China) Ltd., 720 Cai Lun Road, Pudong, Shanghai, 201203, China.
  • Tomas Racek
    Roche Innovation Centre, Basel, Switzerland F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
  • Gadissa Bedada Hundie
    Department of Viroscience, Erasmus Medical Center, Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
  • Yong Lin
    Department of Psychogeriatrics, Kangci Hospital of Jiaxing, Tongxiang, Zhejiang, China.
  • Charles A Boucher
    Department of Viroscience, Erasmus Medical Center, Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
  • David van de Vijver
    Department of Viroscience, Erasmus Medical Center, Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
  • Bart L Haagmans
    Department of Viroscience, Erasmus Medical Center, Rotterdam, 's-Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands. b.haagmans@erasmusmc.nl.