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Published on: May 26, 2013
Reconstruction of viral population structure from next-generation sequencing data using multicommodity flows
Pavel Skums1, Nicholas Mancuso, Alexander Artyomenko
1Laboratory of Molecular Epidemiology and Bioinformatics, Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road NE, 30333 Atlanta, GA, USA. kki8@cdc.gov
BMC Bioinformatics
|August 2, 2013
Summary
Two new methods, AmpMCF and ShotMCF, accurately reconstruct viral quasispecies populations from next-generation sequencing (NGS) data. These Multicommodity Flow (MCF)-based approaches improve the analysis of viral evolution and drug resistance.
Area of Science:
- Virology
- Computational Biology
- Genomics
Background:
- Highly mutable RNA viruses exist as complex quasispecies populations within hosts.
- Next-generation sequencing (NGS) offers powerful tools for analyzing viral populations.
- Accurate reconstruction of intra-host viral genetic composition remains a significant challenge.
Purpose of the Study:
- To develop accurate computational methods for reconstructing viral quasispecies from NGS data.
- To estimate the frequencies of individual viral variants within a host population.
Main Methods:
- Developed two novel methods, AmpMCF and ShotMCF, based on Multicommodity Flows (MCFs).
- AmpMCF is designed for amplicon-based NGS reads, utilizing a covering formulation.
- ShotMCF is designed for shotgun NGS reads, employing a packing formulation.
Main Results:
- Both AmpMCF and ShotMCF demonstrated high accuracy in reconstructing viral population structures.
- The methods accurately estimated quasispecies frequencies, particularly with large datasets.
- Performance was evaluated against state-of-the-art algorithms like Maximum Bandwidth and ViSpA.
Conclusions:
- The MCF formulation effectively solves the problem of viral population reconstruction from NGS reads.
- AmpMCF and ShotMCF provide accurate tools for analyzing intra-host viral population dynamics.
- Software implementations are publicly available for research use.
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