Evidence map›Paper›PMID 24284629›Full record

ArticleNature2014

Mutational and fitness landscapes of an RNA virus revealed through population sequencing.

Ashley Acevedo, Leonid Brodsky, Raul Andino

Abstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers.

0numbers the graph read from it
0cells of the map it votes in
251citing papers in PubMed
27.4field-weighted citation impact, top 1% of its field
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

251 citing papers in PubMed, 428 citations in OpenAlex.

  1. Review
  2. Molecular therapy. Nucleic acids · 2026
    Article
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191 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Ashley AcevedoDepartment of Microbiology and Immunology, University of California, San Francisco, California 94122-2280, USA.
Leonid BrodskyTauber Bioinformatics Research Center and Department of Evolutionary & Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
Raul AndinoDepartment of Microbiology and Immunology, University of California, San Francisco, California 94122-2280, USA.
University of Haifa · IL

Funding

Unbiased Functional Characterization of Enterovirus-Host InteractionsP01AI091575 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2011 to 2015
$10.5M
RNA PROTEIN INTERACTIONS IN POLIOVIRUS REPLICATIONR01AI040085 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 1998 to 2019
$5.8M
RECOMBINANT PICORNAVIRUSES AS AIDS VACCINESR01AI036178 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 1994 to 2011
$3.6M
Genetic Diversity as a determinant of viral adaptation and pathogenesisR56AI036178 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 2014 to 2014
$531k
RECOMBINANT PICORNAVIRUSES AS AIDS VACCINESR21AI036178 · NIAID · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI ANDINO, RAUL · 2000 to 2000
$347k
RNA PROTEIN INTERACTIONS IN POLIOVIRUS REPLICATIONR21AI040085 · NIAID · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI ANDINO, RAUL · 1996 to 1996
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NIAID NIH HHS AI091575NIAID NIH HHS AI36178NIAID NIH HHS N01 AI040085NIAID NIH HHS P01 AI091575NIAID NIH HHS R01 AI036178NIAID NIH HHS R01 AI040085NIAID NIH HHS R21 AI036178NIAID NIH HHS R56 AI036178
6 · The paper itself

Abstract

RNA viruses exist as genetically diverse populations. It is thought that diversity and genetic structure of viral populations determine the rapid adaptation observed in RNA viruses and hence their pathogenesis. However, our understanding of the mechanisms underlying virus evolution has been limited by the inability to accurately describe the genetic structure of virus populations. Next-generation sequencing technologies generate data of sufficient depth to characterize virus populations, but are limited in their utility because most variants are present at very low frequencies and are thus indistinguishable from next-generation sequencing errors. Here we present an approach that reduces next-generation sequencing errors and allows the description of virus populations with unprecedented accuracy. Using this approach, we define the mutation rates of poliovirus and uncover the mutation landscape of the population. Furthermore, by monitoring changes in variant frequencies on serially passaged populations, we determined fitness values for thousands of mutations across the viral genome. Mapping of these fitness values onto three-dimensional structures of viral proteins offers a powerful approach for exploring structure-function relationships and potentially uncovering new functions. To our knowledge, our study provides the first single-nucleotide fitness landscape of an evolving RNA virus and establishes a general experimental platform for studying the genetic changes underlying the evolution of virus populations.

Indexed as

DNA Mutational AnalysisEvolution, MolecularGenetic FitnessHeLa CellsHumansModels, MolecularMutationMutation RatePoliovirusQuality ControlStructure-Activity Relationship

Identifiers

PMID24284629
PMCPMC4111796
OpenAlexW1972928030

What OpenQuestion holds

Textmetadata
LicenceTDM
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.