Challenges in the analysis of viral metagenomes

Rose, Rebecca; Constantinides, Bede; Tapinos, Avraam; Robertson, David L; Prosperi, Mattia

Although exhaustive BLAST-like methods can detect homology in divergent sequences, these methods are in general limited by the relatively few validated viral sequences deposited in public databases, the high diversity within viral families which can obscure relatedness, and the lack of a defined set of core genes common to all viruses that can be used to distinguish species (e.g. the 16S gene for bacteria) (Fancello, Raoult, and Desnues 2012) . These features make it difficult to assign similarity thresholds for classification that are applicable to all potential viruses in a sample (Simmonds 2015) . Comparison methods that do not rely on sequence similarity include PhyloPythia (McHardy et al. 2007 ), which uses nucleotide frequencies to classify reads, and PHYMM (Brady and Salzberg 2009) , which uses interpolated Markov models to find variable length oligonucleotides that characterize species in the NCBI RefSeq database.