Mapping the drivers of within-host pathogen evolution using massive data sets

Palmer, Duncan S.; Turner, Isaac; Fidler, Sarah; Frater, John; Goedhals, Dominique; Goulder, Philip; Huang, Kuan-Hsiang Gary; Oxenius, Annette; Phillips, Rodney; Shapiro, Roger; Vuuren, Cloete van; McLean, Angela R.; McVean, Gil

As D B is very large, we can assume that D B represents the collection of viral sequences (subject to recombination) that a host can be infected with. A large number of sequences in D B results in short coalescence times between any given member of D and D B , increasing our power to estimate parameters. By making this approximation, we may then assume that selection along the lineage joining a given member d of D to its nearest neighbour in D B occurred within the individual from whom the virus d was sampled. We have associated host HLA profiles for D, and so may then estimate HLA-associated selection conditional on this HLA information. A cartoon of this model is shown in Figure 1b .