Evidence map›Paper›PMID 26408523›Full record

ArticleMethods (San Diego, Calif.)2015

CoVaMa: Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data.

Andrew Routh, Max W Chang, Jason F Okulicz, John E Johnson, Bruce E Torbett

Open access · greenAbstract read
In one paragraph

Article in Methods (San Diego, Calif.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  9. MiDRMViruses · 2019
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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

5 authors at 4 institutions in 1 country.

Andrew RouthDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA. Electronic address: arouth@scripps.edu.
Max W ChangIntegrative Genomics and Bioinformatics Core, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jason F OkuliczInfectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX 78234, USA; Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
John E JohnsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bruce E TorbettDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: betorbet@scripps.edu.
Scripps Research Institute · USSalk Institute for Biological Studies · USThe University of Texas Medical Branch at Galveston · USUniformed Services University of the Health Sciences · US

Funding

Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
Project 9P50GM103368 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI LEVY, RONALD · 2012 to 2016
$20.0M
STRUCTURE-BASED MECHANISMS FOR RESISTANCE TO PROTEASE INHIBITORSP01GM083658 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI OLSON, ARTHUR J. · 2008 to 2012
$9.6M
Studies of large and small-scale virus capsid dynamicsR01GM054076 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI JOHNSON, JOHN EMIL · 1995 to 2014
$6.2M
MOLECULAR BASIS OF VIRAL PATHOGENESIST32AI007354 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 1989 to 2020
$5.2M
DATA CENTER FOR EPIDEMIOLOGIC INVESTIGATIONS OF HIVN01AI005072 · NIAID · NEW ENGLAND RESEARCH INSTITUTES, INC. · PI MCKINLAY, SONJA M · 1990 to 1994
–
NCATS NIH HHS 5UL1TR001114NCATS NIH HHS UL1 TR001114NIAID NIH HHS T32 AI007354NIAID NIH HHS T32AI007354NIAID NIH HHS Y01 AI005072NIAID NIH HHS Y1-AI-5072NIGMS NIH HHS 1P50GM103368NIGMS NIH HHS 5R01-GM54076NIGMS NIH HHS P01 GM083658NIGMS NIH HHS P50 GM103368NIGMS NIH HHS R01 GM054076
6 · The paper itself

Abstract

Next-Generation Sequencing (NGS) has transformed our understanding of the dynamics and diversity of virus populations for human pathogens and model systems alike. Due to the sensitivity and depth of coverage in NGS, it is possible to measure the frequency of mutations that may be present even at vanishingly low frequencies within the viral population. Here, we describe a simple bioinformatic pipeline called CoVaMa (Co-Variation Mapper) scripted in Python that detects correlated patterns of mutations in a viral sample. Our algorithm takes NGS alignment data and populates large matrices of contingency tables that correspond to every possible pairwise interaction of nucleotides in the viral genome or amino acids in the chosen open reading frame. These tables are then analysed using classical linkage disequilibrium to detect and report evidence of epistasis. We test our analysis with simulated data and then apply the approach to find epistatically linked loci in Flock House Virus genomic RNA grown under controlled cell culture conditions. We also reanalyze NGS data from a large cohort of HIV infected patients and find correlated amino acid substitution events in the protease gene that have arisen in response to anti-viral therapy. This both confirms previous findings and suggests new pairs of interactions within HIV protease. The script is publically available at http://sourceforge.net/projects/covama.

Indexed as

Genome, ViralHigh-Throughput Nucleotide SequencingLinkage DisequilibriumMutationAlgorithmsEpistasis, GeneticHIVHIV InfectionsHumansRNA, ViralSequence Analysis, RNARNA, ViralCovariationFlock House VirusHuman immunodeficiency virus proteaseLinkage disequilibriumRNAseq

Identifiers

PMID26408523
PMCPMC4684750
OpenAlexW2133773193

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.