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1. A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria

Author

Hidayat Trimarsanto, Roberto Amato, Richard D. Pearson, Edwin Sutanto, Rintis Noviyanti, Leily Trianty, Jutta Marfurt, Zuleima Pava, Diego F. Echeverry, Tatiana M. Lopera-Mesa, Lidia M. Montenegro, Alberto Tobón-Castaño, Matthew J. Grigg, Bridget Barber, Timothy William, Nicholas M. Anstey, Sisay Getachew, Beyene Petros, Abraham Aseffa, Ashenafi Assefa, Awab G. Rahim, Nguyen H. Chau, Tran T. Hien, Mohammad S. Alam, Wasif A. Khan, Benedikt Ley, Kamala Thriemer, Sonam Wangchuck, Yaghoob Hamedi, Ishag Adam, Yaobao Liu, Qi Gao, Kanlaya Sriprawat, Marcelo U. Ferreira, Moses Laman, Alyssa Barry, Ivo Mueller, Marcus V. G. Lacerda, Alejandro Llanos-Cuentas, Srivicha Krudsood, Chanthap Lon, Rezika Mohammed, Daniel Yilma, Dhelio B. Pereira, Fe E. J. Espino, Cindy S. Chu, Iván D. Vélez, Chayadol Namaik-larp, Maria F. Villegas, Justin A. Green, Gavin Koh, Julian C. Rayner, Eleanor Drury, Sónia Gonçalves, Victoria Simpson, Olivo Miotto, Alistair Miles, Nicholas J. White, Francois Nosten, Dominic P. Kwiatkowski, Ric N. Price, Sarah Auburn, Pearson, Richard D [0000-0002-7386-3566], Sutanto, Edwin [0000-0002-2997-4648], Marfurt, Jutta [0000-0002-3846-0825], Echeverry, Diego F [0000-0003-0301-4478], Tobón-Castaño, Alberto [0000-0002-1671-2649], Grigg, Matthew J [0000-0001-9914-8352], Alam, Mohammad S [0000-0001-8330-5499], Khan, Wasif A [0000-0002-7650-8068], Ley, Benedikt [0000-0002-5734-0845], Mueller, Ivo [0000-0001-6554-6889], Lacerda, Marcus VG [0000-0003-3374-9985], Pereira, Dhelio B [0000-0002-7761-5498], Espino, Fe EJ [0000-0003-1690-1711], Koh, Gavin [0000-0002-7336-1566], Rayner, Julian C [0000-0002-9835-1014], Drury, Eleanor [0000-0002-9887-6961], Miotto, Olivo [0000-0001-8060-6771], Nosten, Francois [0000-0002-7951-0745], Kwiatkowski, Dominic P [0000-0002-5023-0176], Price, Ric N [0000-0003-2000-2874], Auburn, Sarah [0000-0002-4638-536X], and Apollo - University of Cambridge Repository

Subjects
Likelihood Functions, Internet, Molecular medicine, 45, Epidemiology, 692/308/2056, article, Medicine (miscellaneous), 631/114/1305, General Biochemistry, Genetics and Molecular Biology, 692/4017, Malaria, Genetics research, Machine learning, Malaria, Vivax, 692/699/255/1629, Humans, PLASMODIUM, 692/308/174, Plasmodium vivax, General Agricultural and Biological Sciences
Abstract

Funder: HT was supported by a Charles Darwin University International PhD Scholarship (CDIPS), Funder: Malaysian Ministry of Health (BP00500420), Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.

Published
2022

2. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples

Author

Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Grigg, Matthew J [0000-0001-9914-8352], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [0000-0002-7386-3566], Phyo, Aung P [0000-0002-0383-9624], Price, Ric N [0000-0003-2000-2874], Rayner, Julian C [0000-0002-9835-1014], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository

Subjects
parasitic diseases, Genomics, Genomic Epidemiology, Plasmodium vivax, Malaria, Data Resource
Abstract

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.

Published
2022

3. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples

Author

MalariaGEN, Adam, Ishag, Alam, Mohammad Shafiul, Alemu, Sisay, Amaratunga, Chanaki, Amato, Roberto, Andrianaranjaka, Voahangy, Anstey, Nicholas M, Aseffa, Abraham, Ashley, Elizabeth, Assefa, Ashenafi, Auburn, Sarah, Barber, Bridget E, Barry, Alyssa, Batista Pereira, Dhelio, Cao, Jun, Chau, Nguyen Hoang, Chotivanich, Kesinee, Chu, Cindy, Dondorp, Arjen M, Drury, Eleanor, Echeverry, Diego F, Erko, Berhanu, Espino, Fe, Fairhurst, Rick, Faiz, Abdul, Fernanda Villegas, María, Gao, Qi, Golassa, Lemu, Goncalves, Sonia, Grigg, Matthew J, Hamedi, Yaghoob, Hien, Tran Tinh, Htut, Ye, Johnson, Kimberly J, Karunaweera, Nadira, Khan, Wasif, Krudsood, Srivicha, Kwiatkowski, Dominic P, Lacerda, Marcus, Ley, Benedikt, Lim, Pharath, Liu, Yaobao, Llanos-Cuentas, Alejandro, Lon, Chanthap, Lopera-Mesa, Tatiana, Marfurt, Jutta, Michon, Pascal, Miotto, Olivo, Mohammed, Rezika, Mueller, Ivo, Namaik-Larp, Chayadol, Newton, Paul N, Nguyen, Thuy-Nhien, Nosten, Francois, Noviyanti, Rintis, Pava, Zuleima, Pearson, Richard D, Petros, Beyene, Phyo, Aung P, Price, Ric N, Pukrittayakamee, Sasithon, Rahim, Awab Ghulam, Randrianarivelojosia, Milijaona, Rayner, Julian C, Rumaseb, Angela, Siegel, Sasha V, Simpson, Victoria J, Thriemer, Kamala, Tobon-Castano, Alberto, Trimarsanto, Hidayat, Urbano Ferreira, Marcelo, Vélez, Ivan D, Wangchuk, Sonam, Wellems, Thomas E, White, Nicholas J, William, Timothy, Yasnot, Maria F, Yilma, Daniel, AII - Infectious diseases, Intensive Care Medicine, MalariaGEN, Alam, Mohammad Shafiul [0000-0001-8330-5499], Ashley, Elizabeth [0000-0002-7620-4822], Barber, Bridget E [0000-0003-1066-7960], Batista Pereira, Dhelio [0000-0002-7761-5498], Chu, Cindy [0000-0001-9465-8214], Dondorp, Arjen M [0000-0001-5190-2395], Echeverry, Diego F [0000-0003-0301-4478], Espino, Fe [0000-0003-1690-1711], Faiz, Abdul [0000-0002-3460-7535], Golassa, Lemu [0000-0002-1216-8711], Karunaweera, Nadira [0000-0003-3985-1817], Kwiatkowski, Dominic P [0000-0002-5023-0176], Ley, Benedikt [0000-0002-5734-0845], Miotto, Olivo [0000-0001-8060-6771], Nguyen, Thuy-Nhien [0000-0002-4101-5706], Nosten, Francois [0000-0002-7951-0745], Pearson, Richard D [0000-0002-7386-3566], Phyo, Aung P [0000-0002-0383-9624], Price, Ric N [0000-0003-2000-2874], Rayner, Julian C [0000-0002-9835-1014], Urbano Ferreira, Marcelo [0000-0002-5293-9090], Wellems, Thomas E [0000-0003-3899-8454], Yasnot, Maria F [0000-0001-8081-4212], Yilma, Daniel [0000-0001-6058-2696], and Apollo - University of Cambridge Repository

Subjects
Data resource, parasitic diseases, Medicine (miscellaneous), Genomics, Genomic epidemiology, Plasmodium vivax, General Biochemistry, Genetics and Molecular Biology, Malaria
Abstract

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.

Published
2022

4. Long read assemblies of geographically dispersed Plasmodium falciparum isolates reveal highly structured subtelomeres

Author

Ellen Bruske, Ulrike Böhme, Daouda Ndiaye, Sandra Dimonte, Sarah K. Volkman, Susana Campino, Adam J. Reid, David J. Conway, Mihir Kekre, Matthew Berriman, Abdirahman I. Abdi, Lindsay B. Stewart, Thomas D. Otto, Rick M. Fairhurst, Mandy Sanders, Mahamadou Diakite, Craig W. Duffy, Matthias Franck, Alfred Amambua-Ngwa, Antoine Claessens, Chris I. Newbold, William L Hamilton, Peter C. Bull, Richard D. Pearson, Technische Universität Ilmenau (TU ), The Wellcome Trust Sanger Institute [Cambridge], Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Department of Epidemiology of Parasitic Diseases, Université de Bamako-Malaria Research and Training Centre, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases-National Institutes of Health, Otto, Thomas D [0000-0002-1246-7404], Duffy, Craig W [0000-0001-9359-4888], Bull, Pete C [0000-0002-7674-6752], Pearson, Richard D [0000-0002-7386-3566], Abdi, Abdirahman [0000-0001-7989-2125], Stewart, Lindsay B [0000-0002-9003-0160], Claessens, Antoine [0000-0002-4277-0914], Diakite, Mahamadou [0000-0002-4268-8857], Conway, David J [0000-0002-8711-3037], Newbold, Chris I [0000-0002-9274-3789], Berriman, Matt [0000-0002-9581-0377], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Genome evolution, complete genomes, viruses, Plasmodium falciparum, Medicine (miscellaneous), Genomics, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene family, Long read Assembly, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Copy-number variation, Gene, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], virus diseases, definition of core genome, Articles, biochemical phenomena, metabolism, and nutrition, Subtelomere, digestive system diseases, 3. Good health, 030104 developmental biology, Evolutionary biology, 030217 neurology & neurosurgery, Reference genome, Research Article
Abstract

Background: Although thousands of clinical isolates of Plasmodium falciparum are being sequenced and analysed by short read technology, the data do not resolve the highly variable subtelomeric regions of the genomes that contain polymorphic gene families involved in immune evasion and pathogenesis. There is also no current standard definition of the boundaries of these variable subtelomeric regions. Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated the genomes of 15 P. falciparum isolates, ten of which are newly cultured clinical isolates. We performed comparative analysis of the entire genome with particular emphasis on the subtelomeric regions and the internal var genes clusters. Results: The nearly complete sequence of these 15 isolates has enabled us to define a highly conserved core genome, to delineate the boundaries of the subtelomeric regions, and to compare these across isolates. We found highly structured variable regions in the genome. Some exported gene families purportedly involved in release of merozoites show copy number variation. As an example of ongoing genome evolution, we found a novel CLAG gene in six isolates. We also found a novel gene that was relatively enriched in the South East Asian isolates compared to those from Africa. Conclusions: These 15 manually curated new reference genome sequences with their nearly complete subtelomeric regions and fully assembled genes are an important new resource for the malaria research community. We report the overall conserved structure and pattern of important gene families and the more clearly defined subtelomeric regions.

Published
2018

5. Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax

Author

Nicholas T.Y. Lim, Christoph Q. Schmidt, James M. Murphy, Usheer Kanjee, Marcelo U. Ferreira, Yee-Foong Mok, Michael D. W. Griffin, Kanlaya Sriprawat, Manoj T. Duraisingh, Brian J. Smith, Jonathan Abraham, Bruce Russell, Melissa J. Call, Maria J. Menezes, Gabriel W. Rangel, Laurent Rénia, Wai-Hong Tham, Li Jin Chan, Sebastien Menant, Jakub Gruszczyk, Benoit Malleret, Michael P. Weekes, Kai-Min Lin, Richard D. Pearson, Gruszczyk, Jakub [0000-0003-4536-2964], Kanjee, Usheer [0000-0002-3169-4557], Chan, Li-Jin [0000-0002-9439-3487], Malleret, Benoit [0000-0001-9658-7528], Mok, Yee-Foong [0000-0002-4252-9426], Lin, Kai-Min [0000-0003-2109-1530], Pearson, Richard D [0000-0002-7386-3566], Rangel, Gabriel [0000-0002-8208-2817], Smith, Brian J [0000-0003-0498-1910], Call, Melissa J [0000-0001-7684-5841], Weekes, Michael P [0000-0003-3196-5545], Sriprawat, Kanlaya [0000-0003-2968-1770], Russell, Bruce [0000-0003-2333-4348], Renia, Laurent [0000-0003-0349-1557], Tham, Wai-Hong [0000-0001-7950-8699], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Reticulocytes, medicine.drug_class, 030231 tropical medicine, Plasmodium vivax, Protozoan Proteins, Host tropism, Transferrin receptor, Biology, Monoclonal antibody, Crystallography, X-Ray, Host-Parasite Interactions, 03 medical and health sciences, PLASMODIUM FALCIPARUM, 0302 clinical medicine, Reticulocyte, Protein Domains, Antigens, CD, parasitic diseases, Receptors, Transferrin, medicine, Malaria, Vivax, Humans, Receptor, chemistry.chemical_classification, Multidisciplinary, Membrane Proteins, biology.organism_classification, Molecular biology, 3. Good health, Red blood cell, 030104 developmental biology, medicine.anatomical_structure, chemistry, Transferrin, Gene Knockdown Techniques
Abstract

Vivax malaria host receptor Human malaria is caused by half a dozen species of Plasmodium protozoan parasites, each with distinctive biology. P. vivax , which causes relapsing malaria, specifically parasitizes immature red blood cells called reticulocytes. Gruszczyk et al. identified TfR1 (host transferrin receptor 1) as an alternative receptor for P. vivax . TfR1 binds to a specific P. vivax surface protein. However, the parasite that causes cerebral malaria, P. falciparum , does not share TfR1 as a receptor: P. falciparum could still infect cells in which TfR1 expression was knocked down, but P. vivax could not. Monoclonal antibodies to the P. vivax protein successfully hindered P. vivax infection of red blood cells. Science , this issue p. 48

Published
2018

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