Combinatorial analysis and algorithms for quasispecies reconstruction using next-generation sequencing

Background: Next-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, metagenomics, 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 ...

• Type: Journal
• Year: 2011
• Where: BMCBI
• Authors: Mattia C. F. Prosperi, Luciano Prosperi, Alessandro Bruselles, Isabella Abbate, Gabriella Rozera, Donatella Vincenti, Maria Carmela Solmone, Maria Rosaria Capobianchi, Giovanni Ulivi
• Keywords: Biometrics, BMCBI 2011, Hepatitis B Virus, Reconstruction Algorithm, Throughput Dna