Challenges in the analysis of viral metagenomes

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

The reconstruction of sequencing reads into full length genes and genomes can be performed by means of either referencebased alignment or de novo assembly, a decision dependent on experimental objectives, read length, quality and data complexity. In reference-based approaches, reads are mapped to similar regions of a supplied template genome, a well-studied and computationally efficient process implemented with a suffix array index of the reference genome. In contrast, de novo assembly is computationally exhaustive but important in cases where either a target genome is poorly characterized or reconstruction of genomes of a priori unknown entities in metagenomes is sought, such as in surveillance studies. For short read data, the increased sequence length afforded by assembly can be necessary to distinguish members of highly conserved gene families from one another. Assembly is also widely used for generating whole genome consensus sequences to facilitate analyses of viral variation, and is a typical starting point for analyses of diverse populations of well-characterized viruses. Even where Glossary Contigs: Contiguous nucleotide sequences assembled from multiple overlapping reads.