Related Experiment Video
Updated: Jun 8, 2026
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
A classification model for G-to-A hypermutation in hepatitis B virus ultra-deep pyrosequencing reads
Elizabeth C Reuman1, Severine Margeridon-Thermet, Harrison B Caudill
1Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA. ereuman@stanfordalumni.org
Motivation:
G → A hypermutation is an innate antiviral defense mechanism, mediated by host enzymes, which leads to the mutational impairment of viruses. Sensitive and specific identification of host-mediated G → A hypermutation is a novel sequence analysis challenge, particularly for viral deep sequencing studies. For example, two of the most common hepatitis B virus (HBV) reverse transcriptase (RT) drug-resistance mutations, A181T and M204I, arise from G → A changes and are routinely detected as low-abundance variants in nearly all HBV deep sequencing samples.
Results:
We developed a classification model using measures of G → A excess and predicted indicators of lethal mutation and applied this model to 325 920 unique deep sequencing reads from plasma virus samples from 45 drug treatment-naïve HBV-infected individuals. The 2.9% of sequence reads that were classified as hypermutated by our model included most of the reads with A181T and/or M204I, indicating the usefulness of this model for distinguishing viral adaptive changes from host-mediated viral editing.
Availability:
Source code and sequence data are available at http://hivdb.stanford.edu/pages/resources.html.
Contact:
ereuman@stanfordalumni.org
Supplementary Information:
Supplementary data are available at Bioinformatics online.
