ArticleBMC bioinformatics2011
Combinatorial analysis and algorithms for quasispecies reconstruction using next-generation sequencing.
Article in BMC bioinformatics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed.
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- Molecular evolution methods to study HIV-1 epidemics.Future virology · 2018Review
- Separation and assembly of deep sequencing data into discrete sub-population genomes.Nucleic acids research · 2017Article
- Classifying the evolutionary and ecological features of neoplasms.Nature reviews. Cancer · 2017Review
- A penalized regression approach to haplotype reconstruction of viral populations arising in early HIV/SIV infection.Bioinformatics (Oxford, England) · 2017Article
- MetaGaAP: A Novel Pipeline to Estimate Community Composition and Abundance from Non-Model Sequence Data.Biology · 2017Article
- Estimation of genetic diversity in viral populations from next generation sequencing data with extremely deep coverage.Algorithms for molecular biology : AMB · 2016Article
- Inferring the Clonal Structure of Viral Populations from Time Series Sequencing.PLoS computational biology · 2015Article
- Recombination in viruses: mechanisms, methods of study, and evolutionary consequences.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2015Review
- Comparison of Major and Minor Viral SNPs Identified through Single Template Sequencing and Pyrosequencing in Acute HIV-1 Infection.PloS one · 2015Article
- Estimating HIV-1 fitness characteristics from cross-sectional genotype data.PLoS computational biology · 2014Article
- Full-length haplotype reconstruction to infer the structure of heterogeneous virus populations.Nucleic acids research · 2014Article
- Deep sequencing of evolving pathogen populations: applications, errors, and bioinformatic solutions.Microbial informatics and experimentation · 2014Article
- Viral quasispecies inference from 454 pyrosequencing.BMC bioinformatics · 2013Article
- Empirical validation of viral quasispecies assembly algorithms: state-of-the-art and challenges.Scientific reports · 2013Article
- Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source.BMC biology · 2013Article
- Sequence assembly demystified.Nature reviews. Genetics · 2013Review
- Probabilistic inference of viral quasispecies subject to recombination.Journal of computational biology : a journal of computational molecular cell biology · 2013Article
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9 authors.
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Abstract
backgroundNext-generation sequencing (NGS) offers a unique opportunity for high-throughput genomics and has potential to replace Sanger sequencing in many fields, including de-novo sequencing, re-sequencing, meta-genomics, and characterisation of infectious pathogens, such as viral quasispecies. Although methodologies and software for whole genome assembly and genome variation analysis have been developed and refined for NGS data, reconstructing a viral quasispecies using NGS data remains a challenge. This application would be useful for analysing intra-host evolutionary pathways in relation to immune responses and antiretroviral therapy exposures. Here we introduce a set of formulae for the combinatorial analysis of a quasispecies, given a NGS re-sequencing experiment and an algorithm for quasispecies reconstruction. We require that sequenced fragments are aligned against a reference genome, and that the reference genome is partitioned into a set of sliding windows (amplicons). The reconstruction algorithm is based on combinations of multinomial distributions and is designed to minimise the reconstruction of false variants, called in-silico recombinants.
resultsThe reconstruction algorithm was applied to error-free simulated data and reconstructed a high percentage of true variants, even at a low genetic diversity, where the chance to obtain in-silico recombinants is high. Results on empirical NGS data from patients infected with hepatitis B virus, confirmed its ability to characterise different viral variants from distinct patients.
conclusionsThe combinatorial analysis provided a description of the difficulty to reconstruct a quasispecies, given a determined amplicon partition and a measure of population diversity. The reconstruction algorithm showed good performance both considering simulated data and real data, even in presence of sequencing errors.
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