Exploring the molecular causes of hepatitis B virus vaccination response: an approach with epigenomic and transcriptomic data

BMC Medical Genomics

Christine Nardini²  Weili Yan¹  Yi Cheng¹  Youtao Lu² 

[1]Department of Clinical Epidemiology, Children’s Hospital of Fudan University, Shanghai, PR China

[2]Group of Clinical Genomic Networks, Key Laboratory of Computational Biology, CAS-MPG, Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China

关键词: Omics;    Methylation;    Vaccine;    Hepatitis B virus;   

Others  :  797112
DOI  :  10.1186/1755-8794-7-12

 received in 2013-11-13, accepted in 2014-03-05,  发布年份 2014

【 摘 要 】

Background

Variable responses to the Hepatitis B Virus (HBV) vaccine have recently been reported as strongly dependent on genetic causes. Yet, the details on such mechanisms of action are still unknown. In parallel, altered DNA methylation states have been uncovered as important contributors to a variety of health conditions. However, methodologies for the analysis of such high-throughput data (epigenomic), especially from the computational point of view, still lack of a gold standard, mostly due to the intrinsic statistical distribution of methylomic data i.e. binomial rather than (pseudo-) normal, which characterizes the better known transcriptomic data.

We present in this article our contribution to the challenge of epigenomic data analysis with application to the variable response to the Hepatitis B virus (HBV) vaccine and its most lethal degeneration: hepatocellular carcinoma (HCC).

Methods

Twenty-five infants were recruited and classified as good and non-/low- responders according to serological test results. Whole genome DNA methylation states were profiled by Illumina HumanMethylation 450 K beadchips. Data were processed through quality and dispersion filtering and with differential methylation analysis based on a combination of average methylation differences and non-parametric statistical tests. Results were finally associated to already published transcriptomics and post-transcriptomics to gain further insight.

Results

We highlight 2 relevant variations in poor-responders to HBV vaccination: the hypomethylation of RNF39 (Ring Finger Protein 39) and the complex biochemical alteration on SULF2 via hypermethylation, down-regulation and post-transcriptional control.

Conclusions

Our approach appears to cope with the new challenges implied by methylomic data distribution to warrant a robust ranking of candidates. In particular, being RNF39 within the Major Histocompatibility Complex (MHC) class I region, its altered methylation state fits with an altered immune reaction compatible with poor responsiveness to vaccination. Additionally, despite SULF2 having been indicated as a potential target for HCC therapy, we can recommend that non-responders to HBV vaccine who develop HCC are quickly directed to other therapies, as SULF2 appears to be already under multiple molecular controls in such patients. Future research in this direction is warranted.

【 授权许可】

   
2014 Lu et al.; licensee BioMed Central Ltd.

【 图 表 】

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