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BMC Genomics. 2014;15 Suppl 6:S17. doi: 10.1186/1471-2164-15-S6-S17. Epub 2014 Oct 17.

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.

PMID:
25573168
PMCID:
PMC4240099
DOI:
10.1186/1471-2164-15-S6-S17
[Indexed for MEDLINE]
Free PMC Article

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