Yang Linlin, Yang Xue, Kong Xiangliang, Cao Zhiwei, Zhang Yongyu, Hu Yiyang, Tang Kailin
School of Life Science and Technology, Tongji University, Shanghai, China.
Changhai hospital of traditional Chinese Medicine, Second Military medical university, Shanghai, China.
PLoS One. 2016 May 26;11(5):e0156166. doi: 10.1371/journal.pone.0156166. eCollection 2016.
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.
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.
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.
慢性乙型肝炎(CHB)是最严重的病毒性疾病之一,它使患者终身面临肝硬化和肝细胞癌(HCC)的风险,从而威胁人类健康。尽管已经积累了一些关于CHB中代谢物改变的证据,但其代谢机制仍知之甚少。分析代谢物之间的协变关系可能为CHB患者潜在的代谢发病机制提供新线索。
本研究收集了来自145例CHB患者和23例健康对照的同一受试者的配对尿液和血清样本。系统地对生物流体内部和之间的代谢物协变进行大规模分析,以探索CHB中代谢重编程的潜在生物学证据。引入随机化和相对排名差异以减少不同样本量引起的偏差。更重要的是,通过将差异变化的协变映射到已知代谢途径来解释功能指征。
我们的结果表明CHB患者中与甘氨酸代谢、脂肪酸代谢和三羧酸循环相关的途径发生了重编程。随着进一步改进,协变分析与网络关联研究相结合将为解释临床多组学数据中的功能线索开辟新的途径。