What is the GSU’s Amplicon Toolkit?

The Genomic Surveillance Unit was set up to improve global human health by accelerating the use and impact of genomic surveillance. The Amplicon Toolkit is a core part of our suite of products, tools, and services that empower partners to add genomic information to their decision-making. It’s a flexible framework that allows partners — both large-scale institutions and smaller-scale in-country labs — to produce actionable public health data on malaria parasites.

The genomes of these parasites contain crucial information. With genetic data, you can tell which species of malaria parasite are present, how many different parasite strains there are (also known as “complexity of infection”), where in the world the infection might have come from, and which drugs are likely to work. This information can radically change how effective different control measures will be. There’s little benefit in administering a drug the parasite is resistant to, or closing a border that the parasite didn’t come through.

All of these properties of a malaria infection — species, complexity of infection, source population, and drug resistance ?— can be inferred from just a few hundred short sections of DNA scattered through the genome. Most are single nucleotide polymorphisms (SNPs) —?single letter changes at particular positions.?

While discovering the associations between SNPs and important parasite characteristics requires whole-genome sequencing, amplicon sequencing can take over once the associations are known. This is faster, less expensive, and doesn’t require large sequencers. It also unlocks the ability to monitor changes in these regions of the parasite genome over time. In other words, it enables genomic surveillance.

To scale amplicon sequencing both at the Wellcome Sanger Institute and elsewhere, the GSU has developed the Amplicon Toolkit, a suite of tools and services for genomic surveillance of malaria parasites. It includes support for laboratory set up, training, sequence upload, bioinformatic analysis, data return, and genetic report cards.

The Toolkit is being developed in the GSU at the Sanger Institute, where tens of thousands of malaria parasite samples are sequenced every year.

End-to-end support

More than an instruction manual for a particular lab process, we are developing the Amplicon Toolkit with an end-to-end lens. We’re designing a product that works seamlessly from sample to actionable insight. The toolkit is modular by design: different partners will need different levels of support. As more partners implement the toolkit, more standards will emerge. The goal is to create products that are intuitive, well-supported, and require little customisation to begin working. We are continually improving the toolkit.

How we work with partners

The target users for the GSU Amplicon Toolkit are both public health practitioners and malaria researchers. Our partners in research labs — both at Sanger and around the world — have deep expertise, and many have been contributing to MalariaGEN for more than a decade. These partners are essential to build the toolkit and refine the product. In time, the information produced by the toolkit will feed into public health decision-making.

To be clear, we do not make public health decisions (nor should we!) We see our role as that of development and implementation partners.?

We believe that technology without human capacity is unsustainable, so we support partners with advice, training, troubleshooting, set-up, analysis, lab processes, and anything else that is needed. We aim to help researchers and public health practitioners around the world add the latest genomic information to their existing malaria control, elimination, and research programs.

A whole-team effort

From silicon to pipette and back again, every team in the Genomic Surveillance Unit is involved in creating and refining the toolkit.

Parasite Surveillance

Since the toolkit is primarily a way to produce parasite data, the Parasite Surveillance team is heavily involved. From creating the amplicon panels to designing bioinformatic analyses, this team leads on the scientific and strategic aspects of the Toolkit.

Surveillance Operations

The In-country operations team, through site visits and remote meetings, support partners as they set up sequencing equipment in-country. They help with set-up, validation, procurement, training, and quality control.

Members of the Surveillance Operations team are also responsible for compliance and sample management, ensuring that the correct processes are followed so that data can be returned swiftly.

Implementation Management

The Implementation Management team keep the Amplicon Toolkit project, with its many intricacies, moving forwards.

Digital Systems & Infrastructure?

The Digital Systems & Infrastructure team build and maintain software solutions to support the deployment of the Amplicon Toolkit (for example, the data uploader that partners use to send sequence data for analysis). They are also responsible for the informatics infrastructure that enables large volumes of data to be generated and transformed efficiently.

Data Analysis & Engineering

The Data Analysis & Engineering team turns the raw outputs of sequencers into more actionable information, ready for interpretation by partners and public health decision-makers. They build and maintain the bioinformatic pipelines for the Amplicon toolkit.

Partnerships, Engagement & Growth

The Partnerships, Engagement & Growth team work with partners to understand their needs and to support them as they interact with different parts of the GSU. They help set up studies, understand their training needs, and help communicate findings.

Vector Surveillance

The GSU Amplicon Toolkit is currently a parasite product, but there are plans to develop similar assays and support structures for malaria vector surveillance. The Vector Surveillance team also has deep experience with bioinformatics training, which will form part of the support structures necessary for the Amplicon Toolkit to succeed.