In the past, research into the human genetic factors that affect resistance to malaria has been characterized by multiple research groups each pursuing relatively small studies on their own samples. But the chance of making a discovery, and replicating the finding, is greatly increased if there are effective mechanisms for different research groups to share data and thereby enlarge the number of samples that are studied. The concept of forming a network for sharing data on the genomic epidemiology of malaria — which was to become the Malaria Genomic Epidemiology Network (MalariaGEN) — originated from work that was funded in 2003 by the Bill & Melinda Gates Foundation and by the UK Medical Research Council. The purpose of this funding was to develop web-based software that would allow the integration of clinical and genetic data collected by different research groups. This funding also supported a workshop on the ethical and ownership issues involved in sharing data, which was held in Accra, Ghana, in January 2004 and attended by scientists and clinical researchers from ten research groups in Africa.
MalariaGEN was established in 2005, with joint funding from the Bill & Melinda Gates Foundation (through the Foundation for the National Institutes of Health) and the Wellcome Trust, as part of the Grand Challenges in Global Health initiative28
). The purpose of this joint funding was to discover mechanisms of protective immunity to malaria by combining analysis of human genome variation with large-scale epidemiological studies in malaria-endemic regions. Five objectives necessary for achieving this goal were identified: building a global network for sharing data on the genomic epidemiology of malaria; collecting DNA and clinical data from individuals with different phenotypes of malaria; characterizing genetic variation in populations in malaria-endemic regions; identifying genetic variants that provide protection against severe malaria; and defining the immunological mechanisms by which such genetic variants exert their protective effect.
The group of researchers who came together to tackle these objectives, the MalariaGEN investigators, are mainly leaders of clinical, epidemiological or immunological research projects in malaria-endemic areas, and they contribute samples and data to the MalariaGEN programme. Other MalariaGEN investigators contribute expertise and technical resources related to high-throughput analysis of genomic variation, statistical genetics or biomedical ethics. The host institutions of MalariaGEN investigators, the MalariaGEN partner institutions, are located in 15 malaria-endemic countries and 6 other countries (for additional information, see http://www.malariagen.net/resource/1
), and the institutions in malaria-endemic countries have well-established study sites, where individuals are recruited to participate in research. Most of these study sites are in sub-Saharan Africa: in Burkina Faso, Cameroon, Gambia, Ghana, Kenya, Malawi, Mali, Nigeria, Senegal, Sudan and Tanzania. There are also MalariaGEN study sites in Papua New Guinea, Sri Lanka, Thailand and Vietnam.
To address the complexities involved in setting up such a global research network, MalariaGEN investigators agreed, at an inaugural meeting in Oxford, United Kingdom, in July 2005, to establish the network in four stages. The first stage was to establish a set of principles and processes, agreed by all investigators, to regulate a central resource of DNA samples and phenotypic data (Box 2
and see http://www.malariagen.net/resource/1
). More specifically, this involved standardizing scientific definitions and procedures, enabling partners to gain secure access to the data resource via the Internet, and developing rules about data sharing, intellectual property and appropriate consent.
Box 2. Key elements of MalariaGEN’s policy
MalariaGEN investigators have agreed on a set of principles and processes for sharing samples and data. An important step was to define several Consortial Projects, each of which has a specific objective and project plan (). Investigators can control how their samples and data are used by MalariaGEN by specifying which Consortial Projects they wish to contribute to.
The second stage was to define a core scientific programme of large-scale experiments and statistical analysis, which would use data and expertise from multiple investigators, and the results of which would belong jointly to all of the investigators involved. Projects that are part of this core programme are called Consortial Projects (Box 2
). There are four such projects so far, and each has a specific objective and a plan of action (). After a Consortial Project has been defined, each investigator decides whether he or she wishes to contribute to the project.
MalariaGEN Consortial Projects
The third stage was to find ways of assisting investigators in malaria-endemic countries to develop clinical and epidemiological studies that would advance the core scientific programme. Investigators were invited to submit funding proposals for projects at their study sites that would contribute to Consortial Projects, using the research infrastructure of the local partner institution and founded on the scientific interests and expertise of the local investigators. Funding was allocated after proposals had been reviewed by a group of investigators that represented the network as a whole (with members from Cameroon, Gambia, Ghana, Italy, Kenya, Malawi, Mali, Sri Lanka, Sudan, Tanzania and the United Kingdom). This group evaluated both the scientific design and the feasibility of the clinical and epidemiological studies proposed, taking into account the infrastructure and expertise of the local partner institution and study site.
The fourth stage was to strengthen the capacity to manage data, and to carry out statistical and genetic analyses, at partner institutions in malaria-endemic countries. A fellowship programme in data analysis was established. After an open application process, a data fellow was appointed at each partner institution. Most of the MalariaGEN data fellows work on the team of a MalariaGEN investigator and have responsibilities for managing the team’s data. All data fellows receive training and support in data management, statistical genetics and computing skills. This training is provided by a team of expert statisticians, geneticists and computer programmers who work at the MalariaGEN Resource Centre, which is based at two locations in the United Kingdom, at the University of Oxford and at the Wellcome Trust Sanger Institute near Cambridge. Members of the MalariaGEN resource centre organize regular data-analysis workshops, both in the United Kingdom and at partner institutions in malaria-endemic countries. These workshops provide structured teaching, together with an opportunity for data fellows to share their experiences and to analyse their own data with hands-on assistance from an expert.