Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.

Next generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV env,...

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Autores principales:	Kemal Eren, Steven Weaver, Robert Ketteringham, Morné Valentyn, Melissa Laird Smith, Venkatesh Kumar, Sanjay Mohan, Sergei L Kosakovsky Pond, Ben Murrell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2018
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f6845c2ab3904b2da2c22b7046705531
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spelling	oai:doaj.org-article:f6845c2ab3904b2da2c22b70467055312021-12-02T19:57:35ZFull-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.1553-734X1553-735810.1371/journal.pcbi.1006498https://doaj.org/article/f6845c2ab3904b2da2c22b70467055312018-12-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1006498https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Next generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV env, the protein of interest for HIV vaccine studies, is exceptionally challenging for long-read sequencing and analysis due to its length, high substitution rate, and extensive indel variation. While long-read sequencing is attractive in this setting, the analysis of such data is not well handled by existing methods. To address this, we introduce FLEA (Full-Length Envelope Analyzer), which performs end-to-end analysis and visualization of long-read sequencing data. FLEA consists of both a pipeline (optionally run on a high-performance cluster), and a client-side web application that provides interactive results. The pipeline transforms FASTQ reads into high-quality consensus sequences (HQCSs) and uses them to build a codon-aware multiple sequence alignment. The resulting alignment is then used to infer phylogenies, selection pressure, and evolutionary dynamics. The web application provides publication-quality plots and interactive visualizations, including an annotated viral alignment browser, time series plots of evolutionary dynamics, visualizations of gene-wide selective pressures (such as dN/dS) across time and across protein structure, and a phylogenetic tree browser. We demonstrate how FLEA may be used to process Pacific Biosciences HIV env data and describe recent examples of its use. Simulations show how FLEA dramatically reduces the error rate of this sequencing platform, providing an accurate portrait of complex and variable HIV env populations. A public instance of FLEA is hosted at http://flea.datamonkey.org. The Python source code for the FLEA pipeline can be found at https://github.com/veg/flea-pipeline. The client-side application is available at https://github.com/veg/flea-web-app. A live demo of the P018 results can be found at http://flea.murrell.group/view/P018.Kemal ErenSteven WeaverRobert KetteringhamMorné ValentynMelissa Laird SmithVenkatesh KumarSanjay MohanSergei L Kosakovsky PondBen MurrellPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 14, Iss 12, p e1006498 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Kemal Eren Steven Weaver Robert Ketteringham Morné Valentyn Melissa Laird Smith Venkatesh Kumar Sanjay Mohan Sergei L Kosakovsky Pond Ben Murrell Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
description	Next generation sequencing of viral populations has advanced our understanding of viral population dynamics, the development of drug resistance, and escape from host immune responses. Many applications require complete gene sequences, which can be impossible to reconstruct from short reads. HIV env, the protein of interest for HIV vaccine studies, is exceptionally challenging for long-read sequencing and analysis due to its length, high substitution rate, and extensive indel variation. While long-read sequencing is attractive in this setting, the analysis of such data is not well handled by existing methods. To address this, we introduce FLEA (Full-Length Envelope Analyzer), which performs end-to-end analysis and visualization of long-read sequencing data. FLEA consists of both a pipeline (optionally run on a high-performance cluster), and a client-side web application that provides interactive results. The pipeline transforms FASTQ reads into high-quality consensus sequences (HQCSs) and uses them to build a codon-aware multiple sequence alignment. The resulting alignment is then used to infer phylogenies, selection pressure, and evolutionary dynamics. The web application provides publication-quality plots and interactive visualizations, including an annotated viral alignment browser, time series plots of evolutionary dynamics, visualizations of gene-wide selective pressures (such as dN/dS) across time and across protein structure, and a phylogenetic tree browser. We demonstrate how FLEA may be used to process Pacific Biosciences HIV env data and describe recent examples of its use. Simulations show how FLEA dramatically reduces the error rate of this sequencing platform, providing an accurate portrait of complex and variable HIV env populations. A public instance of FLEA is hosted at http://flea.datamonkey.org. The Python source code for the FLEA pipeline can be found at https://github.com/veg/flea-pipeline. The client-side application is available at https://github.com/veg/flea-web-app. A live demo of the P018 results can be found at http://flea.murrell.group/view/P018.
format	article
author	Kemal Eren Steven Weaver Robert Ketteringham Morné Valentyn Melissa Laird Smith Venkatesh Kumar Sanjay Mohan Sergei L Kosakovsky Pond Ben Murrell
author_facet	Kemal Eren Steven Weaver Robert Ketteringham Morné Valentyn Melissa Laird Smith Venkatesh Kumar Sanjay Mohan Sergei L Kosakovsky Pond Ben Murrell
author_sort	Kemal Eren
title	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
title_short	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
title_full	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
title_fullStr	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
title_full_unstemmed	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.
title_sort	full-length envelope analyzer (flea): a tool for longitudinal analysis of viral amplicons.
publisher	Public Library of Science (PLoS)
publishDate	2018
url	https://doaj.org/article/f6845c2ab3904b2da2c22b7046705531
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Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons.

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