title: Viral diversity and clonal evolution from unphased genomic data.
abstract: BACKGROUND
  Clonal expansion is a process in which a single organism reproduces asexually, giving rise to a diversifying population. It is pervasive in nature, from within-host pathogen evolution to emergent infectious disease outbreaks. Standard phylogenetic tools rely on full-length genomes of individual pathogens or population consensus sequences (phased genotypes).
  
  
  METHODS
  We introduce two measures of diversity to study the evolution of clonal populations using unphased genomic data, which eliminate the need to construct full-length genomes. Our method follows a maximum likelihood approach to estimate evolutionary rates and times to the most recent common ancestor, based on a relaxed molecular clock model; independent of a growth model. Deviations from neutral evolution indicate the presence of selection and bottleneck events.
  
  
  RESULTS
  We evaluated our methods in silico and then compared it against existing approaches with the well-characterized 2009 H1N1 influenza pandemic. We then applied our method to high-throughput genomic data from marburgvirus-infected non-human primates and inferred the time of infection and the intra-host evolutionary rate, and identified purifying selection in viral populations.
  
  
  CONCLUSIONS
  Our method has the power to make use of minor variants present in less than 1% of the population and capture genomic diversification within days of infection, making it an ideal tool for the study of acute RNA viral infection dynamics.
authors.forename: Hossein
authors.initials: H
authors.lastname: Khiabanian
authors.forename: Zachary
authors.initials: Z
authors.lastname: Carpenter
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kugelman
authors.forename: Joseph
authors.initials: J
authors.lastname: Chan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trifonov
authors.forename: Elyse
authors.initials: E
authors.lastname: Nagle
authors.forename: Travis
authors.initials: T
authors.lastname: Warren
authors.forename: Patrick
authors.initials: P
authors.lastname: Iversen
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
mesh_terms: D000465:Algorithms; D000818:Animals; D019143:Evolution, Molecular; D016679:Genome, Viral; D023281:Genomics / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D014780:Viruses / Q000145:classification* / Q000235:genetics*