MalariaGEN - Malaria Genomic Epidemiology Network

MalariaGEN is a data-sharing community working to develop new tools to control malaria by integrating epidemiology with genome science.

Malaria is a disease that afflicts hundreds of millions of people and is a major cause of mortality in the developing world, causing considerable human suffering as well as carrying a massive socioeconomic burden for many of the poorest countries in the world. The disease is caused by Plasmodium parasites that invade human red blood cells and are transmitted from in the blood meals of Anopheles mosquito vectors.

One of the main obstacles to controlling malaria is an evolutionary 'arms race' between the parasite, mosquito and human populations. Parasites and mosquitoes are continually adapting in response to the genetic pressure exerted by disease control methods such as anti-malarial drugs, insecticides and other public health interventions. Human populations exposed to malaria have also acquired genetic changes that help to protect against malaria, however these traits can also be harmful and cause disorders such as sickle cell disease.

The MalariaGEN Genomic Epidemiology Network is a community of researchers in more than 20 countries who are working together to understand how genome variation in human, Plasmodium and Anopheles populations affects the biology and epidemiology of malaria, and to use this knowledge to develop improved tools for malaria control.

[Genome Research Limited]

The Network

MalariaGEN brings together the work of many different partner studies in malaria-endemic regions around the world, each of which is led by an independent investigator and has its own scientific objectives. MalariaGEN adds value to partner studies by providing access to genotyping and sequencing technologies, and by providing a framework for sharing and integrating data in consortial projects and community projects. A key priority of the network is open access data-sharing that allows large-scale collaborative projects to be conducted across multiple populations, bringing together detailed clinical and epidemiological data with state-of-the-art technologies for genome sequencing and web tools for data analysis.

Malian community.

Malian community. [Abdoulaye Djimde]
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Our goals are:

  • To expedite the development of an effective vaccine by discovering human genetic variants that determine natural resistance to malaria, and by discovering Plasmodium genetic mechanisms that enable parasites to evade the human immune system.
  • To develop new approaches for monitoring anti-malarial drug resistance and preventing it spreading, by analysis of Plasmodium genome variation, population structure and recent evolutionary selection.
  • To support innovative strategies for vector control by analysis of Anopheles genome variation, population structure, gene flow, insecticide resistance and anti-parasitic host defence.

Our Work

MalariaGEN provides a platform for malaria researchers around the world to work together on large-scale collaborative projects that combine epidemiology with analysis of genome variation in host, parasite and vector populations. The MalariaGEN community is made up of more than 100 researchers in over 20 countries, working together on projects that involve clinical research, epidemiology, genetics, statistics, parasitology, entomology, immunology, computer science and ethics.

Host Projects:

  • Genetic resistance to severe malaria
  • Genetic determinants of the immune response to malaria
  • Human genome diversity in malaria-endemic regions

Parasite Projects:

  • Plasmodium falciparum population genomics
  • Plasmodium falciparum genetic crosses
  • Plasmodium vivax genome variation

Vector Projects:

  • Anopheles gambiae genome variation

Research capacity building is a vital part of MalariaGEN's mission. We run a data bursary scheme which provides support for researchers in malaria-endemic countries to develop capacity for statistics and genetic data analysis. Most recipients work on a specific partner study and have responsibilities for managing the study's data.

Research in Mali.

Research in Mali. [Abdoulaye Djimde]
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Ethics, Governance and Funding

The work of the network is coordinated by a resource centre whose members are based at Oxford University, the Wellcome Trust Sanger Institute, the London School of Hygiene and Tropical Medicine, and the Wellcome-Mahidol Unit in Bangkok. We provide stewardship of the central resource of samples and data, together with support for sequencing, genotyping, informatics, ethics and capacity building.

The foundations for a data-sharing network in the genomic epidemiology of malaria were developed in 2003-5 with grants from the Medical Research Council and the Gates Foundation. MalariaGEN was formally established in 2005 as part of the Grand Challenges in Global Health initiative, with joint funding from the Wellcome Trust and the Gates Foundation through the Foundation for the National Institutes of Health. The resource centre is primarily funded by the Wellcome Trust, however MalariaGEN brings together partner studies around the world that are funded from a range of sources.

There are many practical and ethical challenges involved in sharing data across a global network comprising investigators and institutions with great disparities in funding and infrastructure. The MalariaGEN community has been working to develop transparent procedures for ethics and governance. We have a governance committee and an independent data access committee, and network policies for data sharing and data access.

Publications

  • Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

    Magnus Manske, Olivo Miotto et al

    Nature 2012

    DOI: 10.1038/nature11174

  • Methodological challenges of genome-wide association analysis in Africa.

    Teo YY, Small KS and Kwiatkowski DP

    Nature reviews. Genetics 2010;11;2;149-60

    PUBMED: 20084087; PMC: 3769612; DOI: 10.1038/nrg2731

  • Ethical data release in genome-wide association studies in developing countries.

    Parker M, Bull SJ, de Vries J, Agbenyega T, Doumbo OK and Kwiatkowski DP

    PLoS medicine 2009;6;11;e1000143

    PUBMED: 19956792; PMC: 2771895; DOI: 10.1371/journal.pmed.1000143

  • Genome-wide and fine-resolution association analysis of malaria in West Africa.

    Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, Kivinen K, Bojang KA, Conway DJ, Pinder M, Sirugo G, Sisay-Joof F, Usen S, Auburn S, Bumpstead SJ, Campino S, Coffey A, Dunham A, Fry AE, Green A, Gwilliam R, Hunt SE, Inouye M, Jeffreys AE, Mendy A, Palotie A, Potter S, Ragoussis J, Rogers J, Rowlands K, Somaskantharajah E, Whittaker P, Widden C, Donnelly P, Howie B, Marchini J, Morris A, SanJoaquin M, Achidi EA, Agbenyega T, Allen A, Amodu O, Corran P, Djimde A, Dolo A, Doumbo OK, Drakeley C, Dunstan S, Evans J, Farrar J, Fernando D, Hien TT, Horstmann RD, Ibrahim M, Karunaweera N, Kokwaro G, Koram KA, Lemnge M, Makani J, Marsh K, Michon P, Modiano D, Molyneux ME, Mueller I, Parker M, Peshu N, Plowe CV, Puijalon O, Reeder J, Reyburn H, Riley EM, Sakuntabhai A, Singhasivanon P, Sirima S, Tall A, Taylor TE, Thera M, Troye-Blomberg M, Williams TN, Wilson M, Kwiatkowski DP, Wellcome Trust Case Control Consortium and Malaria Genomic Epidemiology Network

    Nature genetics 2009;41;6;657-65

    PUBMED: 19465909; PMC: 2889040; DOI: 10.1038/ng.388

  • A global network for investigating the genomic epidemiology of malaria.

    Malaria Genomic Epidemiology Network

    Nature 2008;456;7223;732-7

    PUBMED: 19079050; PMC: 3758999; DOI: 10.1038/nature07632

  • Valid consent for genomic epidemiology in developing countries.

    Chokshi DA, Thera MA, Parker M, Diakite M, Makani J, Kwiatkowski DP and Doumbo OK

    PLoS medicine 2007;4;4;e95

    PUBMED: 17455985; PMC: 1876398; DOI: 10.1371/journal.pmed.0040095

  • Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network.

    Taylor T, Olola C, Valim C, Agbenyega T, Kremsner P, Krishna S, Kwiatkowski D, Newton C, Missinou M, Pinder M and Wypij D

    Transactions of the Royal Society of Tropical Medicine and Hygiene 2006;100;7;615-22

    PUBMED: 16551469; PMC: 1459261; DOI: 10.1016/j.trstmh.2005.09.021

* quick link - http://q.sanger.ac.uk/17goxx4i