Distinguishing gene flow between malaria parasite populations.

Measuring gene flow between malaria parasite populations in different geographic locations can provide strategic information for malaria control interventions. Multiple important questions pertaining to the design of such studies remain unanswered, limiting efforts to operationalize genomic surveillance tools for routine public health use. This report examines the use of population-level summaries of genetic divergence (FST) and relatedness (identity-by-descent) to distinguish levels of gene flow between malaria populations, focused on field-relevant questions about data size, sampling, and interpretability of observations from genomic surveillance studies. To do this, we use P. falciparum whole genome sequence data and simulated sequence data approximating malaria populations evolving under different current and historical epidemiological conditions. We employ mobile-phone associated mobility data to estimate parasite migration rates over different spatial scales and use this to inform our analysis. This analysis underscores the complementary nature of divergence- and relatedness-based metrics for distinguishing gene flow over different temporal and spatial scales and characterizes the data requirements for using these metrics in different contexts. Our results have implications for the design and implementation of malaria genomic surveillance studies. Author summary: Malaria is a leading infectious cause of illness and death worldwide. Understanding how malaria parasites are spread between different geographic locations can provide useful information for disease control efforts. Examples include identifying source locations for imported infections in lower-incidence "sink" locations and delineating the routes over which drug-resistant malaria strains disperse across geographic space. Genomic surveillance methods use geolocated genetic sequence data from malaria infections to estimate gene flow and connectivity between parasites populations in different locations. This approach has yielded important insights into patterns of connectivity between malaria populations over local, national, and global scales. However, there are multiple unresolved questions about the design and interpretation of these studies. This study evaluates how much data is needed to distinguish different levels of gene flow between parasite populations ("Are the malaria populations in locations i and j linked by higher or lower connectivity than those in locations k and l?"). We examine data size requirements (including the number of genetic markers and number of individual infections analyzed) for this important, implementation-relevant task across multiple epidemiological scenarios, providing practical guidance for the design and interpretation of similar studies. [ABSTRACT FROM AUTHOR]