Measurements of intrahost viral diversity require an unbiased diversity metric

Zhao, L. and Illingworth, C. J. R. (2019) Measurements of intrahost viral diversity require an unbiased diversity metric. Virus Evolution, 5(1), vey041. (doi: 10.1093/ve/vey041) (PMID:30723551) (PMCID:PMC6354029)

Abstract

Viruses exist within hosts at large population sizes and are subject to high rates of mutation. As such, viral populations exhibit considerable sequence diversity. A variety of summary statistics have been developed which describe, in a single number, the extent of diversity in a viral population; such measurements allow the diversities of different populations to be compared, and the effect of evolutionary forces on a population to be assessed. Here we highlight statistical artefacts underlying some common measures of sequence diversity, whereby variation in the depth of genome sequencing may substantially affect the extent of diversity measured in a viral population, making comparisons of population diversity invalid. Specifically, naive estimation of sequence entropy provides a systematically biased metric, a lower read depth being expected to produce a lower estimate of diversity. The number of polymorphic loci per kilobase of genome is more unpredictably affected by read depth, giving potentially flawed results at lower sequencing depths. We show that the nucleotide diversity statistic π provides an unbiased estimate of diversity in the sense that the expected value of the statistic is equal to the correct value of the property being measured. Our results are of importance for studies interpreting genome sequence data; we describe how diversity may be assessed in viral populations in a fair and unbiased manner.

• Item Type: Articles
• Additional Information: This work was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (grant number 101239/Z/13/Z).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Zhao, L., and Illingworth, C. J. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Virus Evolution
• Publisher: Oxford University Press
• ISSN: 2057-1577
• ISSN (Online): 2057-1577
• Published Online: 30 January 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Virus Evolution 5(1): vey041
• Publisher Policy: Reproduced under a Creative Commons License