Evidence map›Paper›PMID 30543621›Full record

ArticlePLoS computational biology2018

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

Kemal Eren, Steven Weaver, Robert Ketteringham, Morné Valentyn, Melissa Laird Smith, Venkatesh Kumar, Sanjay Mohan, Sergei L Kosakovsky Pond, Ben Murrell

Abstract read
In one paragraph

Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Long-read amplicon denoising.Nucleic acids research · 2019
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kemal ErenBioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA.
Steven WeaverDepartment of Biology and Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, USA.
Robert KetteringhamDivision of Medical Virology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, Western Cape, South Africa.
Morné ValentynDivision of Medical Virology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, Western Cape, South Africa.
Melissa Laird SmithDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-7151-3207
Venkatesh KumarDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Sanjay MohanDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Sergei L Kosakovsky PondDepartment of Biology and Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, USA.
Ben MurrellDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-0393-4445

Funding

LC: HIV Vaccine Trials NetworkUM1AI068618 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Margaret Juliana McElrath · 2011 to 2026
$483.6M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4M
High-throughput Deep Sequencing Assay to Reliably Measure the HIV Reservoir during Antiretroviral TherapyR01AI120009 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2015 to 2019
$3.4M
Modeling Epidemic Infectious Diseases Using Sequence AnalysisU01GM110749 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POND, SERGEI L KOSAKOVSKY · 2014 to 2018
$3.0M
HyPhy: Molecular Evolutionary AnalysesR01GM093939 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI MUSE, SPENCER V., POND, SERGEI L KOSAKOVSKY · 2010 to 2018
$2.5M
Characterizing proviral populations in brain tissuesR33DA041007 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2018 to 2019
$1.4M
Viral sequence and dynamic determinants of antibody breadthR00AI120851 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MURRELL, BENJAMIN SYLVESTER · 2016 to 2017
$493k
Inferring physico-chemical constraints at individual sites in protein evolutionR21AI115701 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WERTHEIM, JOEL OKRENT · 2015 to 2016
$416k
NIAID NIH HHS P30 AI036214NIAID NIH HHS R00 AI120851NIAID NIH HHS R01 AI120009NIAID NIH HHS R21 AI115701NIAID NIH HHS UM1 AI068618NIDA NIH HHS R33 DA041007NIGMS NIH HHS R01 GM093939NIGMS NIH HHS U01 GM110749
6 · The paper itself

Abstract

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.

Indexed as

High-Throughput Nucleotide SequencingPhylogenySequence AlignmentSequence Analysis, DNASoftwareViruses

Identifiers

PMID30543621
PMCPMC6314628

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.