부산대학교 도서관

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. Author summary: In this study we aimed to characterise connectivity between populations of Plasmodium falciparum malaria parasites sampled from five cities on the Colombian-Pacific coast where long-term clonal propagation of P. falciparum is frequent. We found that connectivity along the coast is consistent with accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission and thus presenting a possible opportunity for targeted intervention. Our study makes methodological contributions that could be adapted to analyses of other recombining organisms. Akin to numerous studies in both epidemiology and ecological, to characterise connectivity, we used genetic data and computed estimates of relatedness based on identity-by-descent (IBD). However, unlike previous studies, confidence intervals around relatedness estimates were included in our analyses. This is an important consideration for all studies that plan to use limited genetic data to estimate IBD-based relatedness. To identify groups of clonal parasites and to compare parasite populations across cities, we used methods that avoid thresholds, e.g. of highly-related parasite pairs. Threshold-free methods promote cross-comparison in studies of recombining organisms for which thresholds do not have a clear interpretation (e.g. for malaria parasites, where the frequency of clonal propagation varies in space and time and is not fully understood). [ABSTRACT FROM AUTHOR]