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Assessing biases in phylodynamic inferences in the presence of super-spreaders
Arata Hidano1, M Carolyn Gates2
1EpiCentre, School of Veterinary Science, Massey University, Palmerston North, New Zealand. A.Hidano@massey.ac.nz.
Abstract:
Phylodynamic analyses using pathogen genetic data have become popular for making epidemiological inferences. However, many methods assume that the underlying host population follows homogenous mixing patterns. Nevertheless, in real disease outbreaks, a small number of individuals infect a disproportionately large number of others (super-spreaders). Our objective was to quantify the degree of bias in estimating the epidemic starting date in the presence of super-spreaders using different sample selection strategies. We simulated 100 epidemics of a hypothetical pathogen (fast evolving foot and mouth disease virus-like) over a real livestock movement network allowing the genetic mutations in pathogen sequence. Genetic sequences were sampled serially over the epidemic, which were then used to estimate the epidemic starting date using Extended Bayesian Coalescent Skyline plot (EBSP) and Birth-death skyline plot (BDSKY) models. Our results showed that the degree of bias varies over different epidemic situations, with substantial overestimations on the epidemic duration occurring in some occasions. While the accuracy and precision of BDSKY were deteriorated when a super-spreader generated a larger proportion of secondary cases, those of EBSP were deteriorated when epidemics were shorter. The accuracies of the inference were similar irrespective of whether the analysis used all sampled sequences or only a subset of them, although the former required substantially longer computational times. When phylodynamic analyses need to be performed under a time constraint to inform policy makers, we suggest multiple phylodynamics models to be used simultaneously for a subset of data to ascertain the robustness of inferences.
Insights
Super-spreaders in disease outbreaks can bias epidemic start date estimates. Using multiple phylodynamic models on a data subset can improve accuracy under time constraints.
Area of Science:
- Epidemiology
- Computational Biology
- Population Genetics
Background:
- Phylodynamic analyses are crucial for epidemiological inference but often assume homogenous host mixing.
- Real outbreaks feature super-spreaders, where a few individuals cause many infections, violating this assumption.
- The impact of super-spreading on epidemic modeling accuracy remains an important research question.
Purpose of the Study:
- To quantify the bias in estimating epidemic start dates due to super-spreaders.
- To evaluate the influence of different sampling strategies on these estimates.
- To compare the performance of Extended Bayesian Coalescent Skyline plot (EBSP) and Birth-death skyline plot (BDSKY) models.
Main Methods:
- Simulated 100 epidemics of a fast-evolving virus over a livestock movement network.
- Incorporated genetic mutations and serial sampling of pathogen sequences.
- Estimated epidemic start dates using EBSP and BDSKY models.
Main Results:
- Bias in epidemic start date estimation varied with epidemic conditions, sometimes overestimating duration.
- BDSKY model accuracy decreased with increased super-spreader impact; EBSP accuracy decreased with shorter epidemics.
- Inference accuracy was similar using all or a subset of sequences, but subsets reduced computation time.
Conclusions:
- Super-spreader dynamics introduce bias in phylodynamic analyses, affecting epidemic start date and duration estimates.
- Model choice (EBSP vs. BDSKY) impacts robustness to super-spreading and epidemic length.
- For time-sensitive policy decisions, employing multiple phylodynamic models on a data subset ensures robust inferences.
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