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

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...

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Autores principales: Ratmann, Oliver, Wymant, Chris, Colijn, Caroline, Danaviah, Siva, Essex, Max, Frost, Simon, Gall, Astrid, Gaseitsiwe, Simani, Grabowski, Mary K., Gray, Ronald, Guindon, Stephane, von Haeseler, Arndt, Kaleebu, Pontiano, Kendall, Michelle, Kozlov, Alexey, Manasa, Justen, Minh, Bui Quang, Moyo, Sikhulile, Novitsky, Vlad, Nsubuga, Rebecca, Pillay, Sureshnee, Quinn, Thomas C., Serwadda, David, Ssemwanga, Deogratius, Stamatakis, Alexandros, Trifinopoulos, Jana, Wawer, Maria, Brown, Andy Leigh, de Oliveira, Tulio, Kellam, Paul, Pillay, Deenan, Fraser, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597042/
https://www.ncbi.nlm.nih.gov/pubmed/28540766
http://dx.doi.org/10.1089/aid.2017.0061
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author Ratmann, Oliver
Wymant, Chris
Colijn, Caroline
Danaviah, Siva
Essex, Max
Frost, Simon
Gall, Astrid
Gaseitsiwe, Simani
Grabowski, Mary K.
Gray, Ronald
Guindon, Stephane
von Haeseler, Arndt
Kaleebu, Pontiano
Kendall, Michelle
Kozlov, Alexey
Manasa, Justen
Minh, Bui Quang
Moyo, Sikhulile
Novitsky, Vlad
Nsubuga, Rebecca
Pillay, Sureshnee
Quinn, Thomas C.
Serwadda, David
Ssemwanga, Deogratius
Stamatakis, Alexandros
Trifinopoulos, Jana
Wawer, Maria
Brown, Andy Leigh
de Oliveira, Tulio
Kellam, Paul
Pillay, Deenan
Fraser, Christophe
author_facet Ratmann, Oliver
Wymant, Chris
Colijn, Caroline
Danaviah, Siva
Essex, Max
Frost, Simon
Gall, Astrid
Gaseitsiwe, Simani
Grabowski, Mary K.
Gray, Ronald
Guindon, Stephane
von Haeseler, Arndt
Kaleebu, Pontiano
Kendall, Michelle
Kozlov, Alexey
Manasa, Justen
Minh, Bui Quang
Moyo, Sikhulile
Novitsky, Vlad
Nsubuga, Rebecca
Pillay, Sureshnee
Quinn, Thomas C.
Serwadda, David
Ssemwanga, Deogratius
Stamatakis, Alexandros
Trifinopoulos, Jana
Wawer, Maria
Brown, Andy Leigh
de Oliveira, Tulio
Kellam, Paul
Pillay, Deenan
Fraser, Christophe
author_sort Ratmann, Oliver
collection PubMed
description 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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spelling pubmed-55970422017-11-02 HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences Ratmann, Oliver Wymant, Chris Colijn, Caroline Danaviah, Siva Essex, Max Frost, Simon Gall, Astrid Gaseitsiwe, Simani Grabowski, Mary K. Gray, Ronald Guindon, Stephane von Haeseler, Arndt Kaleebu, Pontiano Kendall, Michelle Kozlov, Alexey Manasa, Justen Minh, Bui Quang Moyo, Sikhulile Novitsky, Vlad Nsubuga, Rebecca Pillay, Sureshnee Quinn, Thomas C. Serwadda, David Ssemwanga, Deogratius Stamatakis, Alexandros Trifinopoulos, Jana Wawer, Maria Brown, Andy Leigh de Oliveira, Tulio Kellam, Paul Pillay, Deenan Fraser, Christophe AIDS Res Hum Retroviruses Epidemiology 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. Mary Ann Liebert, Inc. 2017-11-01 2017-11-01 /pmc/articles/PMC5597042/ /pubmed/28540766 http://dx.doi.org/10.1089/aid.2017.0061 Text en © Oliver Ratmann et al. 2017; Published by Mary Ann Liebert, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Epidemiology
Ratmann, Oliver
Wymant, Chris
Colijn, Caroline
Danaviah, Siva
Essex, Max
Frost, Simon
Gall, Astrid
Gaseitsiwe, Simani
Grabowski, Mary K.
Gray, Ronald
Guindon, Stephane
von Haeseler, Arndt
Kaleebu, Pontiano
Kendall, Michelle
Kozlov, Alexey
Manasa, Justen
Minh, Bui Quang
Moyo, Sikhulile
Novitsky, Vlad
Nsubuga, Rebecca
Pillay, Sureshnee
Quinn, Thomas C.
Serwadda, David
Ssemwanga, Deogratius
Stamatakis, Alexandros
Trifinopoulos, Jana
Wawer, Maria
Brown, Andy Leigh
de Oliveira, Tulio
Kellam, Paul
Pillay, Deenan
Fraser, Christophe
HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title_full HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title_fullStr HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title_full_unstemmed HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title_short HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences
title_sort hiv-1 full-genome phylogenetics of generalized epidemics in sub-saharan africa: impact of missing nucleotide characters in next-generation sequences
topic Epidemiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597042/
https://www.ncbi.nlm.nih.gov/pubmed/28540766
http://dx.doi.org/10.1089/aid.2017.0061
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