A method to avoid errors associated with the analysis of hypermutated viral sequences by alignment-based methods.
The human genome encodes for a family of editing enzymes known as APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like3). They induce context dependent G-to-A changes, referred to as "hypermutation", in the genome of viruses such as HIV, SIV, HBV and endogenous retroviruses. Hypermutation is characterized by aligning affected sequences to a reference sequence. We show that indels (insertions/deletions) in the sequences lead to an incorrect assignment of APOBEC3 targeted and non-target sites. This can result in an incorrect identification of hypermutated sequences and erroneous biological inferences made based on hypermutation analysis.
Infection Analytics, Kirby Institute, UNSW Australia, Sydney, Australia.
Hamid
H
Alinejad-Rokny
Department of Biochemistry, Molecular Biology and Biophysics; Masonic Cancer Center; Institute for Molecular Virology; University of Minnesota, MN, USA. Electronic address: diako@umn.edu.
Diako
D
Ebrahimi
D006801:Humans; D009154:Mutation; D016415:Sequence Alignment; D014780:Viruses / Q000235:genetics*
APOBEC3; Alignment; Hypermutation; Indels (insertions/deletions); Viral sequences