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MERS-CoV spillover at the camel-human interface
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Essential revision 1 #19

Closed evogytis closed 6 years ago

evogytis commented 6 years ago

The population genetic model (the particular form of structured coalescent) is highly idealised and this may influence the quantitative conclusions, although we suspect the conclusions are quite robust qualitatively. This model specifically estimates the rate of a lineage moving between demes going backwards in time; the numbers cited for the camel->human rate is really the rate that a lineage in humans goes to a camel going down the tree. The relationship between these migration rates and the epidemiologically meaningful transmission rate is complex and depends among other things on the ratio of population sizes in both demes. Per-capita transmission rates could be estimated using an epidemiologically structured coalescent model (see e.g. papers by Volz & Rasmussen), which would ideally be stochastic due to bursty dynamics in humans. But this would be a large undertaking and so we suggest that for now the distinction is clarified. Overall, a little more discussion of the complexity and pitfalls when relating idealised population genetic models (like the island model used here) to a noisy nonlinear epidemic like this one might be merited.

evogytis commented 6 years ago

Am I understanding the point correctly that the concern is that our rate estimates relate to the sampled sequences alone rather than the epidemiological rate?

trvrb commented 6 years ago

I think the current textual revisions get most of the way there. However, I think the reviewer makes a really good point that we can't interpret the per-lineage backwards-in-time migration rates as a per-infection rate of transmission from camels to humans (and from humans to camels). I think just adding a caveat sentence to the text stating that rates in current figure S5 (prior) should not be interpreted as direct transmission rates would complete the issue.

Also, cite Volz and Rasmussen in the discussion where you currently cite kuhnert_phylodynamics_2016. Provide a small amount of discussion of what these models additionally attempt to do over the SC model.

trvrb commented 6 years ago

This is great. I would consider the issue resolved. Thanks Gytis.