A classification model for G-to-A hypermutation in hepatitis B virus ultra-deep pyrosequencing reads BIOINFORMATICS Reuman, E. C., Margeridon-Thermet, S., Caudill, H. B., Liu, T., Borroto-Esoda, K., Svarovskaia, E. S., Holmes, S. P., Shafer, R. W. 2010; 26 (23): 2929-2932

Abstract

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.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.Source code and sequence data are available at http://hivdb.stanford.edu/pages/resources.html.ereuman@stanfordalumni.orgSupplementary data are available at Bioinformatics online.

View details for DOI 10.1093/bioinformatics/btq570

View details for Web of Science ID 000284430900001

View details for PubMedID 20937597

View details for PubMedCentralID PMC2982158