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Assessing biases in phylodynamic inferences in the presence of super-spreaders

机译:在超级传播者的存在下评估系统动力学推断的偏见

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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.
机译:利用病原体遗传数据进行植物动力学分析已成为流行病学推断的流行方法。但是,许多方法都假定基础宿主群体遵循均匀的混合模式。然而,在真正的疾病暴发中,少数人感染了不成比例的其他人(超级传播者)。我们的目标是使用不同的样本选择策略,对在存在超级传播者的情况下,估计流行病开始日期的偏倚程度进行量化。我们在真实的牲畜运动网络上模拟了100种假想病原体的流行病(如快速发展的口蹄疫病毒样病毒),允许病原体序列中的基因突变。对该流行病进行了连续的遗传序列采样,然后使用扩展贝叶斯联合天际线图(EBSP)和出生-死亡天际线图(BDSKY)模型来估计流行开始日期。我们的结果表明,偏见程度在不同的流行情况下会有所不同,在某些情况下,对流行持续时间的估计过高。当超级传播器产生较大比例的继发病例时,BDSKY的准确性和精度下降,而当流行病较短时,EBSP的准确性和精确度下降。不管分析是使用所有采样序列还是仅使用它们的子集,推断的准确性都是相似的,尽管前者需要更长的计算时间。当需要在一定时间限制下进行系统动力学分析以告知政策制定者时,我们建议针对部分数据同时使用多个系统动力学模型,以确定推理的可靠性。

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