NGS for Studying Viruses “Beyond the Consensus”
Kim JT (2014) EMBnet.journal 20(Suppl A), e774. http://dx.doi.org/10.14806/ej.20.A.774
High mutation rates in viruses (especially RNA viruses) have profound consequences on viral evolution, including the formation of quasispecies. These have long been studied in theory (Eigen, 1971) and in silico (Wilke et al., 2001). NGS technologies provide new opportunities to directly observe sequence diversity and its evolution in viruses (Wright et al., 2011) and other systems (Schütze et al., 2011).
Profiles of base frequencies can be constructed from virus NGS data. They are used in a number of well established bioinformatics contexts, including DNA binding site representation (Stormo, 2000) and progressive multiple alignment (Larkin et al., 2007). Profiles can be formalised as elements of a continuous sequence space (Vingron and Sibbald, 1993), and they serve as a basis for information theoretic analyses (Schneider et al., 1986; Kim et al., 2003) and statistical learning approaches (Kim et al., 2004).
Figure 1. Continuous sequences as a point of departure for many bioinformatic analyses.
Given this basis, profiles provide a point of departure for many types of analyses of NGS data comprising diverse populations, illustrated in Figure 1. I will demonstrate their construction, outline some opportunities for their future use in studying viral diversity and quasispecies, and discuss technical requirements for their appropriate and efficient use.
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