Model diagnostics and refinement for phylodynamic models
Fig 1
Schematic illustration of the rationale of the marked latent residuals.
Assume that a single pathogen strain enters a host and begins to evolve at time t0. A within-host-diversity model, crudely illustrated by (a), allows for establishment of new strains (i.e. new branches) generated from mutations (occurred at internal nodes). The s-d-s model M0, illustrated by (b), allows only mutations along the (linear) line/branch and as a result assumes only one (dominant) strain at any particular time point. Assume that two sequence samples GA and GB (superscripts dropped without ambiguity) are randomly sampled from the pathogen population at tA and tB respectively, where tA − tB ≈ 0 (i.e. ζ(k) ≈ 1). (a) may predict distinct GA and GB, while (b) would predict minimal difference between them due to the implied linear relationship between mutations and time. Therefore, residuals associated with high ζ(k) may be expected to be large if a model takes insufficient account of within-host-diversity.