High-throughput HIV sequencing: evolution in 2D

Evaluation of: Willerth SM, Pedro HA, Pachter L, Humeau LM, Arkin AP, Schaffer DV: Development of a low bias method for characterizing viral populations using next generation sequencing technology. PLoS ONE 5(10), E13564 (2010). The recent commercialization of high-throughput sequencing technologies has brought about the possibility of characterizing complex viral populations at previously unattainable scales. An important consideration in designing experiments with these technologies is the need for large quantities of input DNA. To accommodate low-input samples, an amplification step is required, usually a PCR, which comes at the risk of introducing a bias that potentially distorts the view of the viral population composition. By implementing a new sample preprocessing protocol, Willerth et al. address these experimental limitations in the context of complete HIV genome sequencing. Moreover, to facilitate the assembly of short and potentially divergent HIV-derived reads, the authors construct a full-length data-specific consensus sequence using a novel bioinformatics approach that capitalizes on the available HIV complete genomes.