Abstract
We developed an algorithm named ViReMa (Viral-Recombination-Mapper) to provide a versatile platform for rapid, sensitive and nucleotide-resolution detection of recombination junctions in viral genomes using next-generation sequencing data. Rather than mapping read segments of pre-defined lengths and positions, ViReMa dynamically generates moving read segments. ViReMa initially attempts to align the 5′ end of a read to the reference genome(s) with the Bowtie seed-based alignment. A new read segment is then made by either extracting any unaligned nucleotides at the 3′ end of the read or by trimming the first nucleotide from the read. This continues iteratively until all portions of the read are either mapped or trimmed. With multiple reference genomes, it is possible to detect virus-to-host or inter-virus recombination. ViReMa is also capable of detecting insertion and substitution events and multiple recombination junctions within a single read. By mapping the distribution of recombination events in the genome of flock house virus, we demonstrate that this information can be used to discover de novo functional motifs located in conserved regions of the viral genome.
Highlights
Viruses are renowned for their ability to mutate and rapidly adapt to new environments
Using ViReMa, we demonstrate that by mapping the distribution and frequency of recombination events in the genome of flock house virus (FHV), we can discover de novo functional genomic motifs required for viral replication and encapsidation
The nature of these trimmed nucleotides is scrutinized in the second phase of the program and is reported according to whether they constitute insertion or substitution events
Summary
Viruses are renowned for their ability to mutate and rapidly adapt to new environments. The use of next-generation sequencing (NGS) has risen dramatically in virus discovery and the identification of emerging pathogens [1,2,3], the characterization of the human virome [4], the analysis of established infectious agents [5,6], the quality control of live attenuated viruses [7,8]. Viral recombination generates considerable genetic diversity and plays a central role in the evolution and emergence of new viruses [11]. Homologous recombination between co-infecting viruses may result in the evolution of new virus strains, as was observed among picornaviruses including human rhinoviruses [12] and between vaccine-derived polioviruses and circulating enteroviruses [13]
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