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Fix molecular clock based on literature search #38

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Nov 1, 2024
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@j23414 j23414 commented Nov 1, 2024

Description of proposed changes

For the West Nile Virus (WNV) global tree, the molecular clock estimates were too low. I searched the literature to find BEAST runs of the global WNV tree estimating average and lineage-based substitution rates per position per year to set the molecular clock in our global and Washington (WA) tree refinement steps. Literature sources are listed in the commit messages.

Before
Screenshot 2024-11-01 at 10 40 43 AM

View current WNV global tree: https://next.nextstrain.org/staging/WNV/genome

After
Screenshot 2024-11-01 at 10 41 35 AM

View fixed WNV global tree: https://next.nextstrain.org/staging/WNV/global
From this key commit: f34b755

I also used a literature search to set the clock rate on the Washington-focused build

View fixed Washington state tree: https://next.nextstrain.org/staging/WNV/WA?m=num_date
From this key commit: bf0ed7c

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j23414 added 11 commits October 31, 2024 09:32
Lanciotti, et al, 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science, 286(5448), pp.2333-2337.
https://www.science.org/doi/epdf/10.1126/science.286.5448.2333
Bakonyi, et al, 2006. Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. Emerging infectious diseases, 12(4), p.618.
https://wwwnc.cdc.gov/eid/article/12/4/05-1379_article
Bakonyi, et al, 2005. Novel flavivirus or new lineage of West Nile virus, central Europe. Emerging infectious diseases, 11(2), p.225.
https://wwwnc.cdc.gov/eid/article/11/2/04-1028_article
Chaintoutis, et al, 2013. West Nile virus lineage 2 strain in Greece, 2012. Emerging infectious diseases, 19(5), p.827.
https://wwwnc.cdc.gov/eid/article/19/5/12-1418_article
Platonov, et al, 2001. Outbreak of West Nile virus infection, Volgograd Region, Russia, 1999. Emerging infectious diseases, 7(1), p.128.
https://wwwnc.cdc.gov/eid/article/7/1/70-0128_article
From May et al, 2011 "Phylogeography of West Nile Virus: From the Cradle of Evolution in Africa to Eurasia, Australia, and the Americas"
https://journals.asm.org/doi/10.1128/jvi.01963-10

"The mean rate of nucleotide substitution among all isolates of WNV is 7.55 x 10^-4
substitutions/site/year...This rate is comparable to that previously estimated for other
flaviviruses...WNV show some heterogeneity among different genotypes, but all groups
have various rates of between 2.24 x 10^-4 substitutions/site/year ... and 1.06 x 10^-3."

Fixing the clock-rate at 0.00075 results in MRCA in auspice tree between 1600-1700 which matches the literature
from Fall et al, 2017 "Biological and phylogenetic characteristics of West African lineages of West Nile virus"
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006078

"The tMRCA of WNV is predicted to have originated in the late 16th/early 17th century (95%HPD: 1476–1765)"
From May et al, 2011 "Phylogeography of West Nile Virus: From the Cradle of Evolution in Africa to Eurasia, Australia, and the Americas"
https://journals.asm.org/doi/10.1128/jvi.01963-10

Table 1, IS98-STD and North America 6.53E-04
@j23414 j23414 linked an issue Nov 1, 2024 that may be closed by this pull request
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j23414 commented Nov 1, 2024

Consulted with @DOH-LMT2303 regarding the modifications. We compared our results to another repository that used a slightly different molecular clock rate (2e-4 instead of 7e-4). Despite this difference, both rates are of the same order of magnitude (10^-4) and represent an improvement over the original rate of 1.4e-5.

Based on this discussion, we've decided to proceed with merging these changes, considering them an enhancement to the current setup. If needed, we can make additional refinements in future pull requests.

@j23414 j23414 merged commit 20237ec into main Nov 1, 2024
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@j23414 j23414 deleted the add-annotations branch November 1, 2024 22:26
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Fix molecular clock in global tree
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