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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Automated, phylogeny-based genotype delimitation of the Hepatitis Viruses HBV and HCV
Dora Serdari1, Evangelia-Georgia Kostaki2, Dimitrios Paraskevis2
1The Exelixis Lab, Scientific Computing Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany.
Insights
Computational methods can automate hepatitis virus classification, moving beyond subjective criteria. Tools like mPTP and ABGD successfully identified genetic clusters corresponding to known hepatitis B virus (HBV) and hepatitis C virus (HCV) genotypes.
Area of Science:
- Virology
- Computational Biology
- Bioinformatics
Background:
- Hepatitis virus classification traditionally relies on subjective, ad hoc criteria like phenotypic traits and arbitrary genetic distances.
- The increasing discovery of new strains and sequencing data makes manual classification cumbersome and difficult to generalize.
Purpose of the Study:
- To evaluate the applicability of computational molecular species delimitation methods for hepatitis virus classification.
- To compare the performance of the mPTP and ABGD tools for classifying hepatitis B virus (HBV) and hepatitis C virus (HCV).
Main Methods:
- Utilized two well-studied hepatitis virus datasets: HBV and HCV.
- Applied computational methods for molecular species delimitation, including mPTP and ABGD, to aligned sequence data.
- ABGD was used to automatically identify the barcoding gap using pairwise genetic distances.
Main Results:
- The mPTP tool accurately identified taxonomic clusters corresponding to known HBV and HCV genotypes, subtypes, and subgenotypes without parameter adjustment.
- ABGD analysis results varied with parameters but showed similarity to mPTP and established taxonomy under specific settings.
- The overlap between predicted clusters and acknowledged genotypes suggests successful automation of virus classification.
Conclusions:
- Computational methods, specifically mPTP and ABGD, demonstrate significant potential for automating hepatitis virus classification.
- These methods offer a more objective and scalable approach compared to traditional subjective criteria.
- Successful application to HBV and HCV classification paves the way for broader use in viral taxonomy.
Background:
The classification of hepatitis viruses still predominantly relies on ad hoc criteria, i.e., phenotypic traits and arbitrary genetic distance thresholds. Given the subjectivity of such practices coupled with the constant sequencing of samples and discovery of new strains, this manual approach to virus classification becomes cumbersome and impossible to generalize.
Methods:
Using two well-studied hepatitis virus datasets, HBV and HCV, we assess if computational methods for molecular species delimitation that are typically applied to barcoding biodiversity studies can also be successfully deployed for hepatitis virus classification. For comparison, we also used ABGD, a tool that in contrast to other distance methods attempts to automatically identify the barcoding gap using pairwise genetic distances for a set of aligned input sequences.
Results—Discussion:
We found that the mPTP species delimitation tool identified even without adapting its default parameters taxonomic clusters that either correspond to the currently acknowledged genotypes or to known subdivision of genotypes (subtypes or subgenotypes). In the cases where the delimited cluster corresponded to subtype or subgenotype, there were previous concerns that their status may be underestimated. The clusters obtained from the ABGD analysis differed depending on the parameters used. However, under certain values the results were very similar to the taxonomy and mPTP which indicates the usefulness of distance based methods in virus taxonomy under appropriate parameter settings. The overlap of predicted clusters with taxonomically acknowledged genotypes implies that virus classification can be successfully automated.

