ViReMa: A Virus Recombination Mapper of Next-Generation Sequencing data characterizes diverse recombinant viral nucleic acids

Abstract

Genetic recombination is a tremendous source of intra-host diversity in viruses and is critical for their ability to rapidly adapt to new environments or fitness challenges. While viruses are routinely characterized using high-throughput sequencing techniques, characterizing the genetic products of recombination in next-generation sequencing data remains a challenge. Viral recombination events can be highly diverse and variable in nature, including simple duplications and deletions, or more complex events such as copy/snap-back recombination, inter-virus or inter-segment recombination and insertions of host nucleic acids. Due to the variable mechanisms driving virus recombination and the different selection pressures acting on the progeny, recombination junctions rarely adhere to simple canonical sites or sequences. Furthermore, numerous different events may be present simultaneously in a viral population, yielding a complex mutational landscape. We have previously developed an algorithm called ViReMa (Virus Recombination Mapper) that bootstraps the bowtie short-read aligner to capture and annotate a wide-range of recombinant species found within virus populations. Here, we have updated ViReMa to provide an 'error-density' function designed to accurately detect recombination events in the longer reads now routinely generated by the Illumina platforms and provide output reports for multiple types of recombinant species using standardized formats. We demonstrate the utility and flexibility of ViReMa in different settings to report deletion events in simulated data from Flock House virus, copy-back RNA species in Sendai viruses, short duplication events in HIV, and virus to host recombination in an archaeal DNA virus.

Characterization of SARS-CoV-2 genetic evolution in vaccinated and non-vaccinated patients from the Kenyan population

“…Recombination events were evaluated to determine SARS-CoV-2 genetic evolution in vaccinated and non-vaccinated patients. We used ViReMa, a viral recombination mapper that identifies intrahost recombination events including deletions, insertions, duplication, copy-back, snap-back, and viral-host chimeric events as described previously 18 , 36 , 37 .…”

“…Virus-Recombination-Mapper (ViReMa; v0.25) was used to identify and quantify recombination events (insertions, deletion, and duplication) 18 , 36 , 37 . We used paired-end next-generation sequence data to detect recombination junction events in the SARS-CoV-2 reference genome.…”

ViReMaShiny: An Interactive Application for Analysis of Viral Recombination Data

“…The Shiny framework provides interactivity, extensibility, and flexibility with local and web-hosted options available. Initial input of user files requires BED files, an output of the ViReMa (Sotcheff, et al, 2022) or other recombination mappers and are hosted locally. Either a single BED file or multiple BED files from multiple biological or experimental replicates can be uploaded.…”

Genome comparison of long-circulating field CnmeGV isolates from the same region

“…To detect whether there were defective viral genomes caused by large deletions in the population, the mapping distance of paired reads was examined. Then the soft-clipped reads were extracted and used to determine the position of individual deletion junctions with the ViReMa ( Sotcheff et al, 2023 ). The junctions were plotted on a circular map using Circos ( Krzywinski et al, 2009 ).…”