HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences - LIRMM - Laboratoire d’Informatique, de Robotique et de Microélectronique de Montpellier Access content directly
Journal Articles AIDS Research and Human Retroviruses Year : 2017

HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

Chris Wymant
  • Function : Author
Caroline Colijn
  • Function : Author
Siva Danaviah
  • Function : Author
Max Essex
  • Function : Author
Simon Frost
  • Function : Author
Astrid Gall
  • Function : Author
Mary Grabowski
  • Function : Author
Ronald Gray
  • Function : Author
Arndt von Haeseler
  • Function : Author
Pontiano Kaleebu
  • Function : Author
Michelle Kendall
  • Function : Author
Alexey Kozlov
Justen Manasa
  • Function : Author
Bui Quang Minh
  • Function : Author
Vlad Novitsky
  • Function : Author
Rebecca Nsubuga
  • Function : Author
Sureshnee Pillay
  • Function : Author
Thomas Quinn
  • Function : Author
David Serwadda
  • Function : Author
Deogratius Ssemwanga
  • Function : Author
Alexandros Stamatakis
Jana Trifinopoulos
  • Function : Author
Maria Wawer
  • Function : Author
Andy Leigh Brown
  • Function : Author
Christophe Fraser
  • Function : Author

Abstract

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n = 2,833; MRC/UVRI Uganda, n = 701; Mochudi Prevention Project, n = 359; Africa Health Research Institute Resistance Cohort, n = 92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3′ end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences (NGS) has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.
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lirmm-01800302 , version 1 (25-05-2018)

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Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, Max Essex, et al.. HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences. AIDS Research and Human Retroviruses, 2017, 33 (11), pp.1083-1098. ⟨10.1089/aid.2017.0061⟩. ⟨lirmm-01800302⟩
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