The power of collaborative genomic discovery

The Neuroscience Institute’s Clinical Omics and Informatics (COIN) Unit, led by Dr Melissa Nel, has a research mantra of “collaborative discovery”, which will be demonstrated in their upcoming solvathon event on 21 and 22 November. At this event, researchers, doctors, bioinformaticians and genetic counsellors will come together to tackle 16 “hard-to-solve” rare-disease cases.

For many patients living with suspected genetic disorders, the search for a diagnosis can be long, complex and emotionally exhausting. Even with advances in genome sequencing technologies, many cases remain unsolved after years of genetic testing and clinical investigation. These are often referred to as “hard-to-solve” cases, meaning the answer may exist within the genome, but uncovering it requires more than a single test, a single technology or a single expert.

The COIN Unit believes that solving these cases requires collaboration. This year, they will host a Genomics Solvathon: a multidisciplinary event designed to bring together clinicians, genetic counsellors, laboratory scientists, bioinformaticians and researchers to collectively investigate difficult-to-diagnose cases, using an advanced approach called high-fidelity (HiFi) long-read sequencing technology.

As part of the solvathon, 16 selected cases will undergo PacBio HiFi long-read whole genome sequencing. Unlike conventional short-read sequencing, long-read technology generates much longer stretches of DNA sequence, allowing researchers to more accurately identify complex forms of genetic variation and better resolve difficult regions of the genome. For unresolved cases, long-read sequencing offers an opportunity to revisit the genome with a new lens through the improved detection of previously missed variation such as large structural variants or repeat expansions.

Why a solvathon?

A solvathon creates an environment where expertise can converge around a shared goal in real time: finding answers for individuals and families who remain without a diagnosis. For many of these cases, the answer may already be present in the data, but hidden: a cryptic variant, an overlooked region, a signal too subtle to recognise clearly. Rather than analysing cases in isolation, the solvathon model encourages collaborative interpretation and discussion. As Dr Nel puts it, “A solvathon is not just about finding answers – it is about bringing the right people and tools together so that answers within reach are no longer ones that get missed.”
 

“A solvathon is not just about finding answers – it is about bringing the right people and tools together so that answers within reach are no longer ones that get missed.”

Clinicians contribute detailed phenotypic insights, laboratory scientists provide technical expertise, and bioinformaticians take large, complex genome sequencing datasets through computational pipelines to surface and interrogate the variation that matters, while researchers explore novel or emerging mechanisms that may explain disease. This multidisciplinary approach is especially valuable in rare and unresolved disease cases, where solving the puzzle may depend on combining multiple perspectives.

The bigger picture 

Beyond solving individual cases, the solvathon offers a glimpse of something larger. The room itself is the point: clinicians, laboratory scientists, genetic counsellors, bioinformaticians and researchers working side by side are exactly the workforce that delivering genomic medicine in South Africa will require. The solvathon models that workforce on a small scale – a single event, a focused set of cases – but it points toward a much larger vision of how genomic medicine could be built and sustained here.

Each unresolved case also contributes to something cumulative: a deeper understanding of human genetic diversity, of disease mechanisms, and of where existing diagnostic frameworks fall short for African patients. By studying African genomes and developing ancestry-aware approaches to interpretation, we can improve diagnostic equity and build tools that work better for African populations. And by bringing people together to learn from one another the solvathon strengthens the training, collaboration and knowledge-sharing that local expertise depends on. “Solve one case, and a family finds an answer. Build the workforce, the data and the tools to solve many, and a country moves closer to genomic medicine that serves everyone,” said Nel.

Looking forward

Not every case will immediately receive a diagnosis. In genomics, progress is often incremental, and some answers take years to emerge – a variant that means little today may become interpretable as reference data grows and understanding deepens. An unsolved case is rarely a closed one.

At its core, the COIN Solvathon is about collaboration, expertise and hope: bringing together people, technologies and skills to tackle cases that have remained unsolved for too long. Because sometimes, solving the hardest cases requires more than sequencing alone. It requires a community willing to work together in pursuit of answers.

Participate in the solvathon.