title: Covariation Analysis of Serumal and Urinary Metabolites Suggests Aberrant Glycine and Fatty Acid Metabolism in Chronic Hepatitis B.
abstract: BACKGROUND
  Chronic hepatitis b (CHB) is one of the most serious viral diseases threatening human health by putting patients at lifelong risk of cirrhosis and hepatocellular carcinoma (HCC). Although some proofs of altered metabolites in CHB were accumulated, its metabolic mechanism remains poorly understood. Analyzing covariations between metabolites may provide new hints toward underlying metabolic pathogenesis in CHB patients.
  
  
  METHODS
  The present study collected paired urine and serum samples from the same subjects including 145 CHB and 23 healthy controls. A large-scale analysis of metabolites' covariation within and across biofluids was systematically done to explore the underlying biological evidences for reprogrammed metabolism in CHB. Randomization and relative ranking difference were introduced to reduce bias caused by different sample size. More importantly, functional indication was interpreted by mapping differentially changed covariations to known metabolic pathways.
  
  
  RESULTS
  Our results suggested reprogrammed pathways related to glycine metabolism, fatty acids metabolism and TCA cycle in CHB patients. With further improvement, the covariation analysis combined with network association study would pave new alternative way to interpret functional clues in clinical multi-omics data.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Linlin
authors.identifier: http://orcid.org/0000-0002-2849-700X
authors.initials: L
authors.lastname: Yang
authors.affiliation: Changhai hospital of traditional Chinese Medicine, Second Military medical university, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Kong
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.|Advanced Institute of Translational Medicine, Tongji University, Shanghai, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D016022:Case-Control Studies; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000032:analysis*; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000652:urine* / Q000821:virology; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D005998:Glycine