Hi Gina & Mahan,
A couple of thoughts on this analysis -
- Although the Hulseberg et al rate might seem the most relevant, as it is for BDBV, those authors are using the divergence between the previous two outbreaks and thus they are essentially getting a rate for the evolution of the virus in the reservoir species (it is notable this is the slowest rate of them all). It is problematic enough that we are using rates from one virus species to calibrate another, differences in host species is likely to be the greater effect.
- Some of the rates are not independent - Hoenen et al (once they fixed their erroneously low rate in the erratum) is the same data as Gire et al with the addition of 2 (epidemiologically linked) genomes from Mali.
- Finding the maximum overlapping interval in the HPDs of the TMRCA under these different rates as the best estimate for the TMRCA is artificially reducing the uncertainty in the estimate by clipping the HPDs - i.e., the more variation there is in the collated rates from the literature, the smaller this overlap will be and the appearance of precision will increase.
- Furthermore, the inclusion of the estimates for the low rates will bias this considerably back in time – excluding Hulseberg et al and Ghafari et al (an unpublished analysis) would make the HPD overlap region considerably more recent and wider.
- Or equally, if the Hulseberg et al rate is the closest to reality (because it is the same virus species, despite being a different host species) then including the faster EBOV rates would bias the estimate towards the present day.
Our similar analysis, done with a slightly larger dataset and using two of the same rate estimates from the literature (Gire et al and Holmes et al to represent a range for rates observed at different stages in the same epidemic), takes the approach of considering the union of the HPDs for these rate possibilities. This is, in my view, a more appropriate representation of the bounds of our knowledge of the TMRCA at this stage. These rates from the literature are not independent estimates of the same quantity but rather alternative possibilities as to what the true underlying rate for this epidemic could be.