title: De novo assembly of highly diverse viral populations.
abstract: BACKGROUND
  Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage.
  
  
  RESULTS
  We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software.
  
  
  CONCLUSIONS
  We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. xiaoyang@broadinstitute.org
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Patrick
authors.initials: P
authors.lastname: Charlebois
authors.forename: Sante
authors.initials: S
authors.lastname: Gnerre
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Coole
authors.forename: Niall J
authors.initials: NJ
authors.lastname: Lennon
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Levin
authors.forename: James
authors.initials: J
authors.lastname: Qu
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ryan
authors.forename: Michael C
authors.initials: MC
authors.lastname: Zody
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Henn
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D016679:Genome, Viral / Q000235:genetics*; D012984:Software