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      Detecting geospatial patterns of Plasmodium falciparum parasite migration in Cambodia using optimized estimated effective migration surfaces

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          Abstract

          Background

          Understanding the genetic structure of natural populations provides insight into the demographic and adaptive processes that have affected those populations. Such information, particularly when integrated with geospatial data, can have translational applications for a variety of fields, including public health. Estimated effective migration surfaces (EEMS) is an approach that allows visualization of the spatial patterns in genomic data to understand population structure and migration. In this study, we developed a workflow to optimize the resolution of spatial grids used to generate EEMS migration maps and applied this optimized workflow to estimate migration of Plasmodium falciparum in Cambodia and bordering regions of Thailand and Vietnam.

          Methods

          The optimal density of EEMS grids was determined based on a new workflow created using density clustering to define genomic clusters and the spatial distance between genomic clusters. Topological skeletons were used to capture the spatial distribution for each genomic cluster and to determine the EEMS grid density; i.e., both genomic and spatial clustering were used to guide the optimization of EEMS grids. Model accuracy for migration estimates using the optimized workflow was tested and compared to grid resolutions selected without the optimized workflow. As a test case, the optimized workflow was applied to genomic data generated from P. falciparum sampled in Cambodia and bordering regions, and migration maps were compared to estimates of malaria endemicity, as well as geographic properties of the study area, as a means of validating observed migration patterns.

          Results

          Optimized grids displayed both high model accuracy and reduced computing time compared to grid densities selected in an unguided manner. In addition, EEMS migration maps generated for P. falciparum using the optimized grid corresponded to estimates of malaria endemicity and geographic properties of the study region that might be expected to impact malaria parasite migration, supporting the validity of the observed migration patterns.

          Conclusions

          Optimized grids reduce spatial uncertainty in the EEMS contours that can result from user-defined parameters, such as the resolution of the spatial grid used in the model. This workflow will be useful to a broad range of EEMS users as it can be applied to analyses involving other organisms of interest and geographic areas.

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          Most cited references36

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          A new world malaria map: Plasmodium falciparum endemicity in 2010

          Background Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Methods Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfR c of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.
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            The Genomic History of Southeastern Europe

            Farming was first introduced to Europe in the mid-7th millennium BCE–associated with migrants from Anatolia who settled in the Southeast before spreading throughout Europe. To understand the dynamics of this process, we analyzed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12,000 and 500 BCE. We document a West-East cline of ancestry in indigenous hunter-gatherers and–in far-eastern Europe–early stages in the formation of Bronze Age Steppe ancestry. We show that the first farmers of northern and western Europe passed through southeastern Europe with limited hunter-gatherer admixture, but that some groups that remained mixed extensively, without the male-biased hunter-gatherer admixture that prevailed later in the North and West. Southeastern Europe continued to be a nexus between East and West, with intermittent genetic contact with the Steppe up to 2000 years before the migrations that replaced much of northern Europe’s population.
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              Visualizing spatial population structure with estimated effective migration surfaces

              Genetic data often exhibit patterns broadly consistent with “isolation by distance” – a phenomenon where genetic similarity decays with geographic distance. In a heterogeneous habitat this may occur more quickly in some regions than others: for example, barriers to gene flow can accelerate differentiation between neighboring groups. We use the concept of “effective migration” to model the relationship between genetics and geography: in this paradigm, effective migration is low in regions where genetic similarity decays quickly. We present a method to visualize variation in effective migration across the habitat from geographically indexed genetic data. Our approach uses a population genetic model to relate effective migration rates to expected genetic dissimilarities. We illustrate its potential and limitations using simulations and data from elephant, human and A. thaliana populations. The resulting visualizations highlight important spatial features of population structure that are difficult to discern using existing methods for summarizing genetic variation.
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                Author and article information

                Contributors
                liyao@umd.edu
                ashetty@som.umaryland.edu
                ChanthapL.ca@afrims.org
                Michele.spring.ctr@afrims.org
                david.l.saunders.mil@mail.mil
                Mark.Fukuda.mil@afrims.org
                hientt@oucru.org
                sasithon.puk@mahidol.ac.th
                rickfairhurst1@gmail.com
                arjen@tropmedres.ac
                chris.plowe@duke.edu
                timothydoconnor@gmail.com
                stakala@medicine.umaryland.edu
                stewartk@umd.edu
                Journal
                Int J Health Geogr
                Int J Health Geogr
                International Journal of Health Geographics
                BioMed Central (London )
                1476-072X
                10 April 2020
                10 April 2020
                2020
                : 19
                : 13
                Affiliations
                [1 ]GRID grid.164295.d, ISNI 0000 0001 0941 7177, Center for Geospatial Information Science, Department of Geographical Sciences, , University of Maryland, ; College Park, 20742 MD USA
                [2 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Duke Global Health Institute, , Duke University, ; Durham, 27710 NC USA
                [3 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Institute for Genome Sciences, , University of Maryland School of Medicine, ; Baltimore, 21201 MD USA
                [4 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Center for Vaccine Development and Global Health, , University of Maryland School of Medicine, ; Baltimore, 21201 MD USA
                [5 ]GRID grid.413910.e, ISNI 0000 0004 0419 1772, Armed Forces Research Institute of Medical Sciences, ; Bangkok, Thailand
                [6 ]GRID grid.412433.3, ISNI 0000 0004 0429 6814, Oxford University Clinical Research Unit, ; Ho Chi Minh City, Vietnam
                [7 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Clinical Tropical Medicine, , Mahidol University, ; Bangkok, Thailand
                [8 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, National Institutes of Health, ; Bethesda, MD USA
                [9 ]GRID grid.501272.3, ISNI 0000 0004 5936 4917, Mahidol-Oxford Tropical Medicine Research Unit, ; Bangkok, Thailand
                Article
                207
                10.1186/s12942-020-00207-3
                7149848
                32276636
                6acd627a-e787-4975-a6f9-f9c5ea6c0206
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 November 2019
                : 1 April 2020
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases of the National Institutes of Health
                Award ID: U19AI129386
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-AI125579
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Public health
                plasmodium falciparum,estimated effective migration surfaces,parasite migration,malaria elimination

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