The GenCoE-PAGRA African WGS Moonshot Project is a pilot initiative designed to sequence at least 25,000 whole genomes (WGS) from African samples to advance genomic research and medicine on the continent. It is a collaboration between Genomics Centres of Excellence in Africa (GenCoE) and the Partnership for Advancing Genomic Research in Africa (PAGRA), supported by Roche and other partners.

The project aims to enhance Africa’s capacity in genomics, address global health disparities, and support the development of medicines tailored to African genetic diversity. The GenCoE-PAGRA African WGS Moonshot Project is designed to advance genomic research by conducting whole genome sequencing (WGS) in Africa, ensuring that samples remain on the continent. It prioritizes maximum access to genomic data for African scientists, empowering them to lead biomedical research while retaining ownership of their samples and data. The initiative supports research and development efforts aimed at creating pharmaceuticals and diagnostics optimized for African populations. To ensure responsible data management, the project establishes a controlled access framework via the European Genome-Phenome Archive (EGA), with governance overseen by the H3Africa Data and Biospecimen Access Committee (DBAC). Additionally, a two-year publication embargo is implemented to safeguard the rights of the researchers generating the data.

The sample providers for the GenCoE-PAGRA African WGS Moonshot Project were identified primarily from H3Africa researchers and African investigators who had previously contributed biological samples for genomic studies. Samples were selected based on existing consent agreements, ensuring that data sharing and secondary use were permitted without restrictions on pharmaceutical applications. Additionally, providers with ongoing sample collection efforts could contribute if their samples reached sequencing facilities within the project's timeframe. The selection process emphasized diverse representation of African genomic data while maintaining ethical standards and participant anonymity.

Access to the genomic data is controlled by the H3Africa Data and Biospecimen Access Committee (DBAC), which oversees data access after submission to the European Genome-Phenome Archive (EGA). GenCoE Leadership and Sample Providers also play a role in facilitating access before public release, ensuring compliance with ethical and regulatory requirements. The Sample Providers are free to make decisions on opening access to other academic groups or individuals in Africa; however, there will be restrictions in place for sharing with pharmaceutical companies that are not PAGRA partners for two years from the time the final WGS data is generated.

All genomic data will be stored securely on the African continent, with access most likely provided through a Trusted Research Environment. Data protection includes: storage in secure facilities on the continent, encryption during transfer and at rest, controlled access mechanisms through data access requests and subsequent Data Access Agreements (DAAs), prohibition on re-identification attempts, anonymized samples with no personally identifiable information shared, and strict contractual restrictions preventing commercial redistribution by pharma partners (limited to internal R&D (research & development) use only).

Data from the GenCoE-PAGRA African WGS Moonshot project will be deposited into the European Genome-phenome Archive (EGA) under controlled access. H3Africa samples will be deposited under the H3Africa Initiative and governed by the H3Africa Data and Biospecimen Access Committee (DBAC). Non-H3Africa samples are encouraged to follow the same governance structure and submit data to the EGA under H3Africa DBAC custodianship.

Following sequencing, the Sample Providers will receive a copy of the sequence data generated from their own samples, and the raw WGS and agreed phenotype data will be shared with approved PAGRA partners, including Roche, for research and development use (in other words, they will share the data with pharma as well as other researchers the Sample providers wish to share with). Phenotype information may be available for the samples, each containing various levels of detail. These will either be in EGA from the original H3Africa data submission or will be requested from the Sample Provider, and where allowed, submitted as new EGA entries linked to the individual sample subsets and can be requested through the access committee. The GenCoE Leadership will apply for access to phenotype data through the H3Africa DBAC for samples from the H3Africa Biorepositories that will be sequenced. The phenotype data will only be available to GenCoE and the Sample Providers for collaborative projects and will be made available to PAGRA members who are funding the sequence data generation. If another requester would like to receive the phenotype data, they must directly contact either the H3Africa DBAC or the Sample Providers.

Participating PAGRA members will access the data at the same time as the African investigators and will agree not to publish for 2 years (the embargo period) to enable primary publication by the African investigators. Participating PAGRA members will continue to be able to access the data after this period. Wider data sharing after the two-year period will be through controlled access managed through a dedicated DAC (H3Africa DBAC) after deposition in the EGA.

Ethical compliance is ensured through: use of samples with appropriate informed consent for data sharing (consent must not restrict commercial entity use), anonymized sample identifiers with prohibition on re-identification, adherence to institutional ethics committees and national regulations, and careful review of clinical data that might identify individuals. Sample Providers are required to obtain ethics approval for use of their samples for this project unless sharing with commercial entities was provided for in the consents of their original projects. Explicit mention of the project should be made in prospective consent forms.

Benefit-sharing includes: African ownership and control of all data, preferential access for African researchers, research infrastructure development on the continent, capacity building through training and workforce development, two-year publication embargo ensuring African investigators publish first, intellectual property ownership by sample providers for their own analyses, and requirement for pharma partners to focus on developing medicines and diagnostics that safely and effectively address African healthcare needs. Through this project African patients can benefit longer term from more effective diagnostics and treatments relevant to their genetic background. As part of the PAGRA/GenCoE collaboration, Pharma partners will provide additional support in the form of specific funds for benefit sharing as part of the agreement. These funds will be allocated for specific community needs and decided upon by the working group and the Joint Steering Committee.

GenCoE is working to ensure ethical pharmaceutical partnerships through PAGRA. This includes comprehensive contractual frameworks (pharma partners receive non-exclusive use rights for internal R&D efforts), prohibition on commercial redistribution, two-year publication embargo protecting African publication rights, annual progress reporting requirements, and adherence to strict ethical governance. Benefit sharing is incorporated through commitment to developing products addressing African healthcare needs and contributing to capacity development. Industry research may contribute to discovery of therapeutic targets and diagnostics, with pharma partners owning IP from their analyses while sample providers retain ownership of their data and IP from their own analyses. PAGRA are also providing legal guidance to ensure that the project complies with consents and data protection laws of the countries involved. The governance framework imposes strict restrictions on the movement and use of the data.

GenCoE aims to build genomics expertise within Africa by ensuring that the sequencing and data processing are conducted on the continent. Part of the GenCoE-PAGRA African WGS Moonshot project includes training in WGS data analysis, and providing support for African investigators to perform their own analysis expeditiously. Additionally, the GenCoE leadership will facilitate collaborative projects with the Sample providers to analyse the complete dataset. These collaborative projects will include mechanisms for capacity development. PAGRA are committed to supporting the development of platforms to ensure storage of the WGS data in Africa and research access by African investigators.

The GenCoE-PAGRA African WGS Moonshot Project will conduct sequencing on the African continent at two primary sites: the Institute of Genomics and Global Health (IGH) in Nigeria and the Centre for Epidemic Response and Innovation (CERI) at Stellenbosch University in South Africa. These centres were selected based on availability of robotics for automated sample processing and capacity for high throughput sequencing.

The GenCoE-PAGRA African WGS Moonshot Project will conduct sequencing on the African continent at two primary sites: the Institute of Genomics and Global Health (IGH) in Nigeria and the Centre for Epidemic Response and Innovation (CERI) at Stellenbosch University in South Africa. These centres were selected based on availability of robotics for automated sample processing and capacity for high throughput sequencing.

Quality control and data processing is conducted in partnership with African investigators at UCT in South Africa and IGH in Nigeria. The project generates comprehensive datasets including joint-called VCF files for all ~25,000 samples, individual gVCF files and CRAM files for individual Sample Provider datasets. Data processing includes alignment to appropriate human reference genomes, variant calling using standard pipelines, and creation of variant annotation databases.

The project uses standardized WGS protocols with Illumina short read technology and potentially Oxford Nanopore long read sequencing where quality permits. All data undergoes quality control, alignment, and variant calling using standard pipelines to ensure consistency across sites.

The GenCoE-PAGRA African WGS Moonshot Project is funded collectively by pharma partners (Roche and additional members) who provide funding for the entire project. While GenCoE continues fundraising to establish centres, this WGS project provides foundational infrastructure and datasets for future translational research applications.

The final joint called VCF file for the 25,000 samples will be available for collaborative projects within the consortium (GenCoE leadership and Sample Providers), and African researchers can request access to the data for research. Once the data are in the EGA all access requests will go through the DBAC. The data will be contributed to the H3Africa reference panel for imputation and the African Genome Variation Database. PAGRA will use the data for R&D.

The project will result in an improved African reference genome panel that better represents the full genetic background of Africa and expands potential to connect African genetic variation to disease. Through alignment and joint calling of the ~25,000 sample cohort, harmonization of phenotypic data, generation of reference panels, and provision of variant frequency data, we will have better resources for novel discoveries on the link between genotype and diseases and the potential for translational research.