MERS-CoV spillover at the camel-human interface
- Fred Hutchinson Cancer Research Center, United States
- University of Edinburgh, United Kingdom
- National Institutes of Health, United States
Figures
Figure 1 with 5 supplements
Typed maximum clade credibility tree of MERS-CoV genomes from 174 human viruses and 100 camel viruses.
Maximum clade credibility (MCC) tree showing inferred ancestral hosts for MERS-CoV recovered with the structured coalescent. The vast majority of MERS-CoV evolution is inferred to occur in camels …
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Figure 1—source data 1
XML to run structured coalescent analysis and output files.
- https://doi.org/10.7554/eLife.31257.009
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Figure 1—source data 2
XML to run structured coalescent analysis with a relaxed prior and output file.
- https://doi.org/10.7554/eLife.31257.010
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Figure 1—source data 3
XML to run discrete trait analysis (DTA) and output files.
- https://doi.org/10.7554/eLife.31257.011
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Figure 1—source data 4
XML to run structured coalescent analysis with equal deme sizes between humans and camels and output files.
- https://doi.org/10.7554/eLife.31257.012
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Figure 1—source data 5
Maximum likelihood phylogeny.
- https://doi.org/10.7554/eLife.31257.013
Figure 1—figure supplement 1
Evolutionary history of MERS-CoV partitioned between camels and humans.
This is the same tree as shown in Figure 1, but with contiguous stretches of MERS-CoV evolutionary history split by inferred host: camels (top in orange) and humans (bottom in blue). This …
Figure 1—figure supplement 2
Posterior backwards migration rate estimates for two choices of prior.
Negligible flow of MERS-CoV lineages from humans into camels is recovered regardless of prior choice (note that rates are backwards in time). Plots show the 95% highest posterior density for the …
Figure 1—figure supplement 3
Maximum clade credibility (MCC) tree with ancestral state reconstruction according to a discrete trait model.
MCC tree is presented the same as Figure 1 and Figure 1—figure supplement 4, with colours indicating the most probable state reconstruction at internal nodes. Unlike the structured coalescent …
Figure 1—figure supplement 4
Maximum clade credibility (MCC) tree of structured coalescent model with enforced equal coalescence rates.
MCC tree is presented the same as Figure 1 and Figure 1—figure supplement 3, with colours indicating the most probable state reconstruction at internal nodes. Similar to Figure 1—figure supplement 3 …
Figure 1—figure supplement 5
Maximum likelihood (ML) tree of MERS-CoV genomes coloured by origin of sequence.
Maximum likelihood tree shows genetic divergence between MERS-CoV genomes collected from camels (orange tips) and humans (blue tips).
Figure 2
Seasonality of MERS-CoV introduction events.
(A) Posterior density estimates partitioned by month showing the 95% highest posterior density interval for relative odds ratios of MERS-CoV introductions into humans. Posterior means are indicated …
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Figure 2—source data 1
MCMC samples from seasonality inference analysis.
- https://doi.org/10.7554/eLife.31257.015
Figure 3 with 6 supplements
Monte Carlo simulations of human transmission clusters.
Leftmost scatter plot shows the distribution of individual Monte Carlo simulation sequence cluster size statistics (mean and skewness) coloured by the value used for the simulation. The dotted …
Figure 3—figure supplement 1
Monte Carlo simulations of human transmission clusters.
From top to bottom each row corresponds to departures from completely random sequencing efforts with respect to case cluster size (bias parameter = 1.0) to sequencing increasingly biased towards …
Figure 3—figure supplement 2
Monte Carlo simulation schematic.
Case clusters are simulated according to Equation 1 until an outbreak size of 2000 cases is reached. We sample 174 cases from each simulation to represent sequencing of human MERS cases. …
Figure 3—figure supplement 3
Results of Monte Carlo simulations with vast underestimation of cases.
The plot is identical to Figure 3—figure supplement 1, but instead of 2000 cases, simulations were run with 4000 cases. With more unobserved cases the R values matching observed MERS-CoV sequence …
Figure 3—figure supplement 4
Boxplots of matching simulated case and sequence cluster distributions.
Boxplots indicate frequency of case (blue, top) and sequence (red, bottom) cluster sizes across simulations at different bias levels, marginalised across values. Outliers are shown with …
Figure 3—figure supplement 5
Quantile-quantile (Q-Q) plot of empirical and simulated sequence cluster sizes.
Density of sequence cluster size percentiles (1 st–99th, calculated across a grid of 50 values) calculated for random states from the posterior distribution (-axis) and matching simulations (-axi…
Figure 3—figure supplement 6
Numbers of epidemiological simulations conforming to empirical observations.
Numbers indicate the total number of epidemiological simulations under each combination of bias and dispersion parameter that result in MERS-CoV-like sequence cluster sizes. More simulations …
Figure 4 with 3 supplements
Recombinant features of MERS-CoV phylogenies.
(A) Marginal posterior probabilities of taxa collected from humans belonging to the same clade in phylogenies derived from different parts of the genome. Taxa are ordered according to phylogeny of …
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Figure 4—source data 1
XML to run structured coalescent analysis on bisected alignment with output files.
- https://doi.org/10.7554/eLife.31257.027
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Figure 4—source data 2
Output from PHI and 3Seq recombination analyses.
- https://doi.org/10.7554/eLife.31257.028
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Figure 4—source data 3
Output from ClonalFrameML analysis.
- https://doi.org/10.7554/eLife.31257.029
Figure 4—figure supplement 1
Tests of recombination across MERS-CoV clades.
Maximum clade credibility tree of MERS-CoV genomes annotated with results of two recombination detection tests (PHI and 3Seq) applied to descendent sequences of each clade. Both tests identify large …
Figure 4—figure supplement 2
MERS-CoV genomes exhibit high numbers of non-clonal loci.
Ancestral state reconstruction (right) identifies a large number of sites in which mutations have occurred more than once in the tree (homoplasies, orange) or are reversions (red) from a state …
Figure 4—figure supplement 3
Human clade sharing between genomic fragments 1 and 2.
Central scatter plot shows the posterior probability of human clades shared between genomic fragments 1 and 2, in their respective trees. Left and bottom scatter plots track the posterior …
Figure 5 with 1 supplement
Demographic history of MERS-CoV in Arabian peninsula camels.
Demographic history of MERS-CoV in camels, as inferred via a skygrid coalescent tree prior (Gill et al., 2013). Three skygrid reconstructions are shown, red and orange for each of the stationary …
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Figure 5—source data 1
XML to run skygrid analysis on camel-like sequence data and output files.
- https://doi.org/10.7554/eLife.31257.032
Figure 5—figure supplement 1
Skygrid comparison between whole and fragmented genomes.
Inferred median recovered using a skygrid tree prior on whole genome (bottom) and ten genomic fragments with independent trees (left), coloured by time. Dotted line indicates the one-to-one line.
Additional files
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Source data 1
MERS-CoV sequences used in the study.
- https://doi.org/10.7554/eLife.31257.033
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Supplementary file 1
Strain names, accessions (where available), identified host and reported collection dates for MERS-CoV genomes used in this study.
- https://doi.org/10.7554/eLife.31257.034
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Transparent reporting form
- https://doi.org/10.7554/eLife.31257.035
