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Identity-by-descent with uncertainty characterises connectivity of Plasmodium falciparum populations on the Colombian-Pacific coast
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-11-16 , DOI: 10.1371/journal.pgen.1009101
Aimee R Taylor 1, 2 , Diego F Echeverry 3, 4, 5 , Timothy J C Anderson 6 , Daniel E Neafsey 2, 7 , Caroline O Buckee 1
Affiliation  

Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonal Plasmodium falciparum samples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation of P. falciparum is frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. Fractions of highly-related sample pairs (whose classification using a threshold accounts for uncertainty) were greater within cities versus between. However, based on both highly-related fractions and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with transmission events involving parasites from five clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude, P. falciparum population connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this hypothesis. For the first time in malaria epidemiology (and to our knowledge in ecological and epidemiological studies more generally), we account for uncertainty around estimated relatedness (an important consideration for studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use threshold-free methods to compare parasite populations and identify clonal components. Threshold-free methods are especially important in analyses of malaria parasites and other recombining organisms with mixed mating systems where thresholds do not have clear interpretation (e.g. due to clonal propagation) and thus undermine the cross-comparison of studies.



中文翻译:


哥伦比亚太平洋沿岸恶性疟原虫种群的连通性具有不确定性的血统特征



表征地理上分离的生物种群之间的连通性是许多领域的共同目标。最近了解疟原虫种群之间的连通性以及对疾病控制工作的影响的方法使用了基于血统身份(IBD)的相关性估计。然而,尚未考虑估计相关性的不确定性。对从哥伦比亚太平洋沿岸五个城市收集的恶性疟原虫单克隆样本对进行了基于 IBD 的不确定性相关性估计,这些城市恶性疟原虫的长期克隆繁殖频繁。这些城市包括布埃纳文图拉和图马科两个官方港口,这两个港口在地理上相隔,但通过频繁的海上交通相连。城市内部与城市之间高度相关的样本对(其分类使用阈值考虑了不确定性)的比例更大。然而,基于高度相关的分数和无阈值方法(寄生虫种群之间的 Wasserstein 距离),布埃纳文图拉和图马科之间的连通性异常高。布埃纳文图拉-图马科的连通性与涉及来自五个克隆成分(在图论框架下识别的统计上无法区分的寄生虫组)的寄生虫的传播事件一致。总而言之,哥伦比亚-太平洋沿岸的恶性疟原虫种群的连通性遵循可及性而非距离隔离,这可能与疟疾传播中的海上交通有关,并为有针对性的干预提供了机会。需要进一步的研究来检验这一假设。 在疟疾流行病学(以及我们在生态和流行病学研究中更广泛的知识)中,我们第一次考虑了估计相关性的不确定性(对于计划使用基因型与全基因组序列数据来估计基于 IBD 的相关性的研究来说,这是一个重要的考虑因素);我们还使用无阈值方法来比较寄生虫种群并识别克隆成分。无阈值方法在分析疟疾寄生虫和其他具有混合交配系统的重组生物体时尤其重要,其中阈值没有明确的解释(例如由于克隆繁殖),从而破坏了研究的交叉比较。

更新日期:2020-11-17
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