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Incorporating Within-Host Diversity in Phylogenetic Analyses for Detecting Clusters of New HIV Diagnoses.


ABSTRACT:

Background

Phylogenetic analyses of HIV sequences are used to detect clusters and inform public health interventions. Conventional approaches summarize within-host HIV diversity with a single consensus sequence per host of the pol gene, obtained from Sanger or next-generation sequencing (NGS). There is growing recognition that this approach discards potentially important information about within-host sequence variation, which can impact phylogenetic inference. However, whether alternative summary methods that incorporate intra-host variation impact phylogenetic inference of transmission network features is unknown.

Methods

We introduce profile sampling, a method to incorporate within-host NGS sequence diversity into phylogenetic HIV cluster inference. We compare this approach to Sanger- and NGS-derived pol and near-whole-genome consensus sequences and evaluate its potential benefits in identifying molecular clusters among all newly-HIV-diagnosed individuals over six months at the largest HIV center in Rhode Island.

Results

Profile sampling cluster inference demonstrated that within-host viral diversity impacts phylogenetic inference across individuals, and that consensus sequence approaches can obscure both magnitude and effect of these impacts. Clustering differed between Sanger- and NGS-derived consensus and profile sampling sequences, and across gene regions.

Discussion

Profile sampling can incorporate within-host HIV diversity captured by NGS into phylogenetic analyses. This additional information can improve robustness of cluster detection.

SUBMITTER: Guang A 

PROVIDER: S-EPMC8891961 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Incorporating Within-Host Diversity in Phylogenetic Analyses for Detecting Clusters of New HIV Diagnoses.

Guang August A   Howison Mark M   Ledingham Lauren L   D'Antuono Matthew M   Chan Philip A PA   Lawrence Charles C   Dunn Casey W CW   Kantor Rami R  

Frontiers in microbiology 20220217


<h4>Background</h4>Phylogenetic analyses of HIV sequences are used to detect clusters and inform public health interventions. Conventional approaches summarize within-host HIV diversity with a single consensus sequence per host of the <i>pol</i> gene, obtained from Sanger or next-generation sequencing (NGS). There is growing recognition that this approach discards potentially important information about within-host sequence variation, which can impact phylogenetic inference. However, whether alt  ...[more]

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