MiRNA-target prediction in hepatitis B virus genome

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About MiRNA-target prediction in hepatitis B virus genome


MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in various cellular processes of post-transcriptional regulation of gene expression. It is known whether miRNAs influence HBV replication by direct binding to viral transcripts. In previous work, a plasma miRNA signature associated with chronic HBV infection was determined (n=86 HBV patients and n=14 healthy controls). It is unknown whether these miRNAs are able to bind to the HBV genome and affect HBV replication. Furthermore, it is unknown whether sequence variations in miRNA binding sites of the viral genome influence the HBV replication efficiency. The aim of this study is to predict miRNA binding, and to identify links between miRNAs and their putative targets in the HBV genome. MicroRNA profiling data and deep sequencing whole HBV genome data obtained from our cohort of chronic HBV infected patients (n=86) will be used for this analysis. For this, existing miRNA target prediction tools will be used, but possibly modifications to these tools or the development of a new target prediction tool may turn out to be needed. The identification of functional miRNAs associated with HBV provides the basis for development of miRNA targeted therapeutic strategies for chronic HBV infection.

As a possible extension, it will be interesting to screen all known human miRNA genes against HBV in order to establish more possible links between miRNAs and targets in the HBV genome. The correlation of these predictions with in-house available miRNA expression data for the same cohort of HBV patients will be analyzed. Furthermore, known sequence variations of HBV in the cohort may be correlated with the location of predicted miRNA targets. Together, differential expression of human miRNAs with predicted targets in HBV, and the presence of sequence variation in those target locations in the HBV genome, will help shed light on the infection and disease mechanisms of HBV, and the interaction with the human host in particular.