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1. Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples [version 1; peer review: 2 approved]

Author

Mohamed Hassan Abdelraheem, Sonia Goncalves, Lemu Golassa, Tim Anderson, Desmond Omane Acheampong, Enoch Aninagyei, Ifeyinwa Aniebo, Patrick O Ansah, Felix Ansah, Gordon A Awandare, Paulo Arnaldo, Maciej F Boni, Gwladys I Bertin, Peter C Bull, Marielle Bouyou-Akotet, Keobouphaphone Chindavongsa, Edwin Kamau, Huch Cheah, Claire Kamaliddin, Vladimir Corredor, David J Conway, Nicholas Day, Abibatou Konaté, Erin Courtier, Theerarat Kochakarn, Arjen Dondorp, Abdoulaye Djimde, Diego F Echeverry, Seydou Doumbia, Mara Lawniczak, Pharath Lim, Sonia Maria Mauricio Enosse, Oumou Maïga-Ascofaré, Thomas G Egwang, Aung Myint Thu, Mark Fleharty, Jutta Marfurt, Caterina A Fanello, Mark Fukuda, Victor Mobegi, Matthew Forbes, Sara Anne Healy, G L Abby Harrison, Anastasia Hernandez-Koutoucheva, Jason A Hendry, Ivo Mueller, Francis Hombhanje, Harald Noedl, Catherine A Hill, Thuy-Nhien Nguyen, Mazza Hussein, Amanda Hott, Rintis Noviyanti, Scott A Jackson, Abraham Oduro, Deus Ishengoma, Harold Ocholla, Julia Jeans, Jean-Bosco Ouedraogo, Chris G Jacob, Drissa S Konate, Jon Keatley, Francois Nosten, Kolapo Oyebola, Myat P Kyaw, Aminatou Kone, Norbert Peshu, Samuel K Lee, Dennis Kyle, Kovana M Loua, Milijaona Randrianarivelojosia, Martha Lemnge, Sasithon Pukrittayakamee, Richard James Maude, Pascal Ringwald, Celine I Mandara, Abdelrahim Osman Mohamed, Toshihiro Mita, Jaqui Montgomery, Julian C Rayner, David Saunders, Olugbenga A Mokuolu, Lastenia Ruiz, Kathryn Murie, Peter Siba, Collins Misita Morang’a, Alex Shayo, Tuyen Nguyen Thi Kim, Thang Ngo Duc, Vincent Ntui-Njock Ntui, Colin Sutherland, Hong Nguyen Van, Xin-zhuan Su, Marie A Onyamboko, Livingstone Tavul, Irene Omedo, Richard Pearson, Antoinette Tshefu, Wellington Aghoghovwia Oyibo, Vandana Thathy, Chris Drakeley, Huynh Hong Quang, Joseph Vinetz, Christopher V Plowe, Federica Verra, Eduard Rovira-Vallbona, Jason Wendler, Anna Rosanas-Urgell, Teun Bousema, Thuy Nguyen, Mahamadou S. Sissoko, Valentin Ruano-Rubio, Alexis Nzila, Shannon Takala-Harrison, Christen Smith, William Yavo, Ngo Viet Thanh, Arthur Talman, Georgia Whitton, Mahamoudou Toure, Rob W van der Pluijm, Sarah Auburn, Antoine Claessens, Mahamadou Diakite, Kesinee Chotivanich, Mehul Dhorda, Olivo Miotto, Mallika Imwong, Mayfong Mayxay, Alfred Amambua-Ngwa, Philip Bejon, Elizabeth Ashley, Alyssa Barry, Rick M. Fairhurst, Ye Htut, Tran Tinh Hien, Kimberly J Johnson, Dominic P Kwiatkowski, Umberto D'Alessandro, Chanthap Lon, Paul N Newton, Aung P Phyo, Ric N Price, Victoria J Simpson, Kevin Marsh, Nicholas J White, Thomas E Wellems, Lynette Isabella Ochola-Oyier, Mozam Ali, Ambroise Ahouidi, Jacob Almagro-Garcia, Ben Andagalu, Lucas Amenga-Etego, Voahangy Andrianaranjaka, Tobias Apinjoh, Vito Baraka, Hampate Ba, Steffen Borrmann, Oralee Branch, Thanat Chookajorn, Souleymane Dama, Chanaki Amaratunga, Alister Craig, Brigitte Denis, Eleanor Drury, Christiane Dolecek, Patrick Duffy, Berhanu Erko, Abdul Faiz, Muzamil Mahdi Abdel Hamid, Anita Ghansah, and Dionicia Gamboa

Subjects
malaria, plasmodium falciparum, genomics, data resource, genomic epidemiology, eng, Medicine, Science
Abstract

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.

Published
2023
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2. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples [version 2; peer review: 2 approved]

Author

MalariaGEN, Ambroise Ahouidi, Mozam Ali, Jacob Almagro-Garcia, Alfred Amambua-Ngwa, Chanaki Amaratunga, Roberto Amato, Lucas Amenga-Etego, Ben Andagalu, Tim J. C. Anderson, Voahangy Andrianaranjaka, Tobias Apinjoh, Cristina Ariani, Elizabeth A Ashley, Sarah Auburn, Gordon A. Awandare, Hampate Ba, Vito Baraka, Alyssa E. Barry, Philip Bejon, Gwladys I. Bertin, Maciej F. Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter C. Bull, George B. J. Busby, Thanat Chookajorn, Kesinee Chotivanich, Antoine Claessens, David Conway, Alister Craig, Umberto D'Alessandro, Souleymane Dama, Nicholas PJ Day, Brigitte Denis, Mahamadou Diakite, Abdoulaye Djimdé, Christiane Dolecek, Arjen M Dondorp, Chris Drakeley, Eleanor Drury, Patrick Duffy, Diego F. Echeverry, Thomas G. Egwang, Berhanu Erko, Rick M. Fairhurst, Abdul Faiz, Caterina A. Fanello, Mark M. Fukuda, Dionicia Gamboa, Anita Ghansah, Lemu Golassa, Sonia Goncalves, William L. Hamilton, G. L. Abby Harrison, Lee Hart, Christa Henrichs, Tran Tinh Hien, Catherine A. Hill, Abraham Hodgson, Christina Hubbart, Mallika Imwong, Deus S. Ishengoma, Scott A. Jackson, Chris G. Jacob, Ben Jeffery, Anna E. Jeffreys, Kimberly J. Johnson, Dushyanth Jyothi, Claire Kamaliddin, Edwin Kamau, Mihir Kekre, Krzysztof Kluczynski, Theerarat Kochakarn, Abibatou Konaté, Dominic P. Kwiatkowski, Myat Phone Kyaw, Pharath Lim, Chanthap Lon, Kovana M. Loua, Oumou Maïga-Ascofaré, Cinzia Malangone, Magnus Manske, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Alistair Miles, Olivo Miotto, Victor Mobegi, Olugbenga A. Mokuolu, Jacqui Montgomery, Ivo Mueller, Paul N. Newton, Thuy Nguyen, Thuy-Nhien Nguyen, Harald Noedl, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Lynette I. Ochola-Oyier, Harold Ocholla, Abraham Oduro, Irene Omedo, Marie A. Onyamboko, Jean-Bosco Ouedraogo, Kolapo Oyebola, Richard D. Pearson, Norbert Peshu, Aung Pyae Phyo, Chris V. Plowe, Ric N. Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Julian C. Rayner, Pascal Ringwald, Kirk A. Rockett, Katherine Rowlands, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Victoria J. Simpson, Jim Stalker, Xin-zhuan Su, Colin Sutherland, Shannon Takala-Harrison, Livingstone Tavul, Vandana Thathy, Antoinette Tshefu, Federica Verra, Joseph Vinetz, Thomas E. Wellems, Jason Wendler, Nicholas J. White, Ian Wright, William Yavo, and Htut Ye

Subjects
Medicine, Science
Abstract

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Published
2021
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3. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples [version 1; peer review: 2 approved]

Author

MalariaGEN, Ambroise Ahouidi, Mozam Ali, Jacob Almagro-Garcia, Alfred Amambua-Ngwa, Chanaki Amaratunga, Roberto Amato, Lucas Amenga-Etego, Ben Andagalu, Tim J. C. Anderson, Voahangy Andrianaranjaka, Tobias Apinjoh, Cristina Ariani, Elizabeth A. Ashley, Sarah Auburn, Gordon Awandare, Hampate Ba, Vito Baraka, Alyssa E. Barry, Philip Bejon, Gwladys I. Bertin, Maciej F. Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter C. Bull, George B. J. Busby, Thanat Chookajorn, Kesinee Chotivanich, Antoine Claessens, David Conway, Alister Craig, Umberto D'Alessandro, Souleymane Dama, Nicholas PJ Day, Brigitte Denis, Mahamadou Diakite, Abdoulaye Djimdé, Christiane Dolecek, Arjen M Dondorp, Chris Drakeley, Eleanor Drury, Patrick Duffy, Diego F. Echeverry, Thomas G. Egwang, Berhanu Erko, Rick M. Fairhurst, Abdul Faiz, Caterina A. Fanello, Mark M. Fukuda, Dionicia Gamboa, Anita Ghansah, Lemu Golassa, Sonia Goncalves, William L. Hamilton, G. L. Abby Harrison, Lee Hart, Christa Henrichs, Tran Tinh Hien, Catherine A. Hill, Abraham Hodgson, Christina Hubbart, Mallika Imwong, Deus S. Ishengoma, Scott A. Jackson, Chris G. Jacob, Ben Jeffery, Anna E. Jeffreys, Kimberly J. Johnson, Dushyanth Jyothi, Claire Kamaliddin, Edwin Kamau, Mihir Kekre, Krzysztof Kluczynski, Theerarat Kochakarn, Abibatou Konaté, Dominic P. Kwiatkowski, Myat Phone Kyaw, Pharath Lim, Chanthap Lon, Kovana M. Loua, Oumou Maïga-Ascofaré, Cinzia Malangone, Magnus Manske, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Alistair Miles, Olivo Miotto, Victor Mobegi, Olugbenga A. Mokuolu, Jacqui Montgomery, Ivo Mueller, Paul N. Newton, Thuy Nguyen, Thuy-Nhien Nguyen, Harald Noedl, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Lynette I. Ochola-Oyier, Harold Ocholla, Abraham Oduro, Irene Omedo, Marie A. Onyamboko, Jean-Bosco Ouedraogo, Kolapo Oyebola, Richard D. Pearson, Norbert Peshu, Aung Pyae Phyo, Chris V. Plowe, Ric N. Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Julian C. Rayner, Pascal Ringwald, Kirk A. Rockett, Katherine Rowlands, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Victoria J. Simpson, Jim Stalker, Xin-zhuan Su, Colin Sutherland, Shannon Takala-Harrison, Livingstone Tavul, Vandana Thathy, Antoinette Tshefu, Federica Verra, Joseph Vinetz, Thomas E. Wellems, Jason Wendler, Nicholas J. White, Ian Wright, William Yavo, and Htut Ye

Subjects
Medicine, Science
Abstract

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Published
2021
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4. Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region.

Author

Leah G Jarsberg, Komal Kedia, Jason Wendler, Aaron T Wright, Paul D Piehowski, Marina A Gritsenko, Tujin Shi, David M Lewinsohn, George B Sigal, Marc H Weiner, Richard D Smith, Joseph Keane, Jon M Jacobs, and Payam Nahid

Subjects
Medicine, Science
Abstract

IntroductionContemporary phase 2 TB disease treatment clinical trials have found that microbiologic treatment responses differ between African versus non-African regions, the reasons for which remain unclear. Understanding host and disease phenotypes that may vary by region is important for optimizing curative treatments.MethodsWe characterized clinical features and the serum proteome of phase 2 TB clinical trial participants undergoing treatment for smear positive, culture-confirmed TB, comparing host serum protein expression in clinical trial participants enrolled in African and Non-African regions. Serum samples were collected from 289 participants enrolled in the Centers for Disease Control and Prevention TBTC Study 29 (NCT00694629) at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment).ResultsAfter a peptide level proteome analysis utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS) and subsequent statistical analysis, a total of 183 core proteins demonstrated significant differences at both baseline and at week 8 timepoints between participants enrolled from African and non-African regions. The majority of the differentially expressed proteins were upregulated in participants from the African region, and included acute phase proteins, mediators of inflammation, as well as coagulation and complement pathways. Downregulated proteins in the African population were primarily linked to nutritional status and lipid metabolism pathways.ConclusionsWe have identified differentially expressed nutrition and lipid pathway proteins by geographic region in TB patients undergoing treatment for pulmonary tuberculosis, which appear to be associated with differential treatment responses. Future TB clinical trials should collect expanded measures of nutritional status and further evaluate the relationship between nutrition and microbiologic treatment response.

Published
2021
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5. Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data.

Author

John D O'Brien, Zamin Iqbal, Jason Wendler, and Lucas Amenga-Etego

Subjects
Biology (General), QH301-705.5
Abstract

We present a rigorous statistical model that infers the structure of P. falciparum mixtures-including the number of strains present, their proportion within the samples, and the amount of unexplained mixture-using whole genome sequence (WGS) data. Applied to simulation data, artificial laboratory mixtures, and field samples, the model provides reasonable inference with as few as 10 reads or 50 SNPs and works efficiently even with much larger data sets. Source code and example data for the model are provided in an open source fashion. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies.

Published
2016
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6. Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein.

Author

Cate Speake, Alexander Pichugin, Tejram Sahu, Vlad Malkov, Robert Morrison, Ying Pei, Laure Juompan, Neta Milman, Stasya Zarling, Charles Anderson, Sharon Wong-Madden, Jason Wendler, Andrew Ishizuka, Zachary W MacMillen, Valentino Garcia, Stefan H I Kappe, Urszula Krzych, and Patrick E Duffy

Subjects
Medicine, Science
Abstract

Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP.

Published
2016
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7. An open dataset of

Author

Ambroise, Ahouidi, Mozam, Ali, Jacob, Almagro-Garcia, Alfred, Amambua-Ngwa, Chanaki, Amaratunga, Roberto, Amato, Lucas, Amenga-Etego, Ben, Andagalu, Tim J C, Anderson, Voahangy, Andrianaranjaka, Tobias, Apinjoh, Cristina, Ariani, Elizabeth A, Ashley, Sarah, Auburn, Gordon A, Awandare, Hampate, Ba, Vito, Baraka, Alyssa E, Barry, Philip, Bejon, Gwladys I, Bertin, Maciej F, Boni, Steffen, Borrmann, Teun, Bousema, Oralee, Branch, Peter C, Bull, George B J, Busby, Thanat, Chookajorn, Kesinee, Chotivanich, Antoine, Claessens, David, Conway, Alister, Craig, Umberto, D'Alessandro, Souleymane, Dama, Nicholas Pj, Day, Brigitte, Denis, Mahamadou, Diakite, Abdoulaye, Djimdé, Christiane, Dolecek, Arjen M, Dondorp, Chris, Drakeley, Eleanor, Drury, Patrick, Duffy, Diego F, Echeverry, Thomas G, Egwang, Berhanu, Erko, Rick M, Fairhurst, Abdul, Faiz, Caterina A, Fanello, Mark M, Fukuda, Dionicia, Gamboa, Anita, Ghansah, Lemu, Golassa, Sonia, Goncalves, William L, Hamilton, G L Abby, Harrison, Lee, Hart, Christa, Henrichs, Tran Tinh, Hien, Catherine A, Hill, Abraham, Hodgson, Christina, Hubbart, Mallika, Imwong, Deus S, Ishengoma, Scott A, Jackson, Chris G, Jacob, Ben, Jeffery, Anna E, Jeffreys, Kimberly J, Johnson, Dushyanth, Jyothi, Claire, Kamaliddin, Edwin, Kamau, Mihir, Kekre, Krzysztof, Kluczynski, Theerarat, Kochakarn, Abibatou, Konaté, Dominic P, Kwiatkowski, Myat Phone, Kyaw, Pharath, Lim, Chanthap, Lon, Kovana M, Loua, Oumou, Maïga-Ascofaré, Cinzia, Malangone, Magnus, Manske, Jutta, Marfurt, Kevin, Marsh, Mayfong, Mayxay, Alistair, Miles, Olivo, Miotto, Victor, Mobegi, Olugbenga A, Mokuolu, Jacqui, Montgomery, Ivo, Mueller, Paul N, Newton, Thuy, Nguyen, Thuy-Nhien, Nguyen, Harald, Noedl, Francois, Nosten, Rintis, Noviyanti, Alexis, Nzila, Lynette I, Ochola-Oyier, Harold, Ocholla, Abraham, Oduro, Irene, Omedo, Marie A, Onyamboko, Jean-Bosco, Ouedraogo, Kolapo, Oyebola, Richard D, Pearson, Norbert, Peshu, Aung Pyae, Phyo, Chris V, Plowe, Ric N, Price, Sasithon, Pukrittayakamee, Milijaona, Randrianarivelojosia, Julian C, Rayner, Pascal, Ringwald, Kirk A, Rockett, Katherine, Rowlands, Lastenia, Ruiz, David, Saunders, Alex, Shayo, Peter, Siba, Victoria J, Simpson, Jim, Stalker, Xin-Zhuan, Su, Colin, Sutherland, Shannon, Takala-Harrison, Livingstone, Tavul, Vandana, Thathy, Antoinette, Tshefu, Federica, Verra, Joseph, Vinetz, Thomas E, Wellems, Jason, Wendler, Nicholas J, White, Ian, Wright, William, Yavo, and Htut, Ye

Subjects
data resource, drug resistance, plasmodium falciparum, parasitic diseases, evolution, malaria, genomics, rapid diagnostic test failure, population genetics, Articles, genomic epidemiology, Research Article
Abstract

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Published
2021

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