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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalMethods
Volume91
DOIs
StatePublished - 2015

Fingerprint

Viruses
Genes
Boidae
HIV Protease
Amino Acids
Viral Genome
RNA Viruses
Linkage Disequilibrium
Pathogens
Mutation Rate
Amino Acid Substitution
Bioinformatics
Computational Biology
Cell culture
Population
Open Reading Frames
Peptide Hydrolases
Substitution reactions
Nucleotides
Cell Culture Techniques

Keywords

  • Covariation
  • Flock House Virus
  • Human immunodeficiency virus protease
  • Linkage disequilibrium
  • RNAseq

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

CoVaMa : Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data. / Routh, Andrew; Chang, Max W.; Okulicz, Jason F.; Johnson, John E.; Torbett, Bruce E.

In: Methods, Vol. 91, 2015, p. 40-47.

Research output: Contribution to journalArticle

Routh, Andrew ; Chang, Max W. ; Okulicz, Jason F. ; Johnson, John E. ; Torbett, Bruce E. / CoVaMa : Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data. In: Methods. 2015 ; Vol. 91. pp. 40-47.
@article{e3714c23f41e41509c141197e44b11da,
title = "CoVaMa: Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data",
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.",
keywords = "Covariation, Flock House Virus, Human immunodeficiency virus protease, Linkage disequilibrium, RNAseq",
author = "Andrew Routh and Chang, {Max W.} and Okulicz, {Jason F.} and Johnson, {John E.} and Torbett, {Bruce E.}",
year = "2015",
doi = "10.1016/j.ymeth.2015.09.021",
language = "English (US)",
volume = "91",
pages = "40--47",
journal = "Methods",
issn = "1046-2023",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - CoVaMa

T2 - Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data

AU - Routh, Andrew

AU - Chang, Max W.

AU - Okulicz, Jason F.

AU - Johnson, John E.

AU - Torbett, Bruce E.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Covariation

KW - Flock House Virus

KW - Human immunodeficiency virus protease

KW - Linkage disequilibrium

KW - RNAseq

UR - http://www.scopus.com/inward/record.url?scp=84961644971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961644971&partnerID=8YFLogxK

U2 - 10.1016/j.ymeth.2015.09.021

DO - 10.1016/j.ymeth.2015.09.021

M3 - Article

VL - 91

SP - 40

EP - 47

JO - Methods

JF - Methods

SN - 1046-2023

ER -