MosaicSolver: a tool for determining recombinants of viral genomes from pileup data.

Graham R Wood,Jessica M Fannon,Eugene V Ryabov,Jonathan D Moore,David J Evans,Nigel Burroughs

doi:10.1093/nar/gku524

Abstract

Viral recombination is a key evolutionary mechanism, aiding escape from host immunity, contributing to changes in tropism and possibly assisting transmission across species barriers. The ability to determine whether recombination has occurred and to locate associated specific recombination junctions is thus of major importance in understanding emerging diseases and pathogenesis. This paper describes a method for determining recombinant mosaics (and their proportions) originating from two parent genomes, using high-throughput sequence data. The method involves setting the problem geometrically and the use of appropriately constrained quadratic programming. Recombinants of the honeybee deformed wing virus and the Varroa destructor virus-1 are inferred to illustrate the method from both siRNAs and reads sampling the viral genome population (cDNA library); our results are confirmed experimentally. Matlab software (MosaicSolver) is available.

Highlights

Recombination provides a mechanism for the rapid evolution of viruses, being implicated in the emergence of many recent pathogenic viral strains in public health and agriculture
Recombination in poliovirus was shown to be associated with ribonucleic acid (RNA) structure and exhibits a GC content bias over an infection cycle [11], whilst protein incompatibility and selection pressure on regulatory, maturation or associated protein functions are likely to add a further layer of selection for the location of recombination points, producing the well-known bias between structural and nonstructural genes [10]
On small interfering RNAs (siRNA) data (21–22-nt reads), we illustrated the basic methodology for determining the composition of a viral population in terms of an unknown number of mosaic genomes, and a refinement technique to locate the recombinant breakpoints

Summary

Introduction

Recombination provides a mechanism for the rapid evolution of viruses, being implicated in the emergence of many recent pathogenic viral strains in public health and agriculture. Human immunodeficiency virus continues to evolve with recombinants predominating in many geographical areas exacerbating control measures [7], whilst recombination has become a focus as a potential risk factor in the use of live attenuated virus vaccines [8] These are all examples of virulence shifts, the recombined virus acquiring new capabilities such as escape from the immune system, drug resistance, increased transmission rates, changes in tissue tropism or acquisition of novel host tropism allowing cross-species transmission. Recent evidence indicates that the recombination mechanism is biphasic, involving distinct crossover and resolution events [12] Mapping these locations is vital for identifying the determinants of recombination and understanding the characteristics of emergent strains. Identification of recombinants within a population of mixed viral genomes, together with their abundance, is a problem of fundamental significance

Methods

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Conclusion