Dr. David Adams: '(The AVE Alliance} is a young, engaging, open community, and one I very much enjoy being a part of.' (Photo courtesy Wellcome Sanger Institute)
[NOTE: David Adams, Ph.D., is a founding member of the Atlas of Variant Effects Alliance and serves as a Senior Group Leader at the Wellcome Sanger Institute in the UK, where he and his team investigate how genetic alterations contribute to cancer development. Adams will be a featured speaker at the Eighth Annual 2025 Mutational Scanning Symposium, May 21 to 23, in Barcelona.]
The Eighth annual MSS Symposium will be in May. Why is this meeting important?
This meeting represents an opportunity to bring together our community of researchers. We discuss the latest advances in research. We also catch up with our colleagues on the work being done as we continue to drive forward this field – this big international field – of variant affects analysis. It’s a young, engaging, open community, and one I very much enjoy being a part of.
The objective of the Atlas of Variant Effects Alliance is to create comprehensive variant effect maps to assist in the diagnosis, prognosis, and treatment of disease. When might such a goal be realized?
The Alliance itself and the development of the technology are relatively young. We have recently established the feasibility of delivering atlases for whole genes and sets of genes, and in parallel, there has been a lot of work to scale variant effect mapping, with the vision being to deploy these methods across the whole genome.
I was at the Sanger Institute at the time the human genome was being sequenced. Over the last two decades I have watched the astronomical improvements in sequencing technology that made this endeavor a reality. I think today, we are exactly at a point in variant effect mapping where the feasibility and the approaches are being established and I imagine we will see several sea changes in the methods we use over the next decade that will allow us to deliver a genome-wide atlas. In 10 to 15 years, we should be able to deliver a variant effect map for all diseases. Of course, we will need financial investment for the technologies to mature.
What will you be presenting on at the symposium in Barcelona?
I am going to talk about how variation impacts cancer disease risk and associated phenotypes. It’s part of an ongoing effort in my research group at the Wellcome Sanger Institute to explore that genetic landscape of cancer predisposition across populations - not just people of European descent, but from other communities around the world. In my presentation, I’m going to describe how our work represents a foundation for a larger effort – to perform variant maps across all cancer genes, as well as other genes. I will also describe how we are developing rich biological readouts, such as single cell sequencing coupled with saturation genome editing, which is allowing us to explore complex phenotypes beyond the classical ‘live-dead’ ones we have used in the past.
One of the AVE Alliance’s goals has been to engage more researchers from the Global South. How can that be achieved?
The approach of the AVE Alliance really does democratize genetics, because we don’t just explore variants found in European populations, but all populations including people from Latin America, Africa, and Asia. In these other regions, there are major human genetic endeavors, and data from the AVE Alliance will greatly complement these studies. To allow scientists from all regions to join the AVE community we need to continue to facilitate their travel, make our content available online, and also continue to think globally when we engage with funders. Ultimately, it comes back to those resources I previously mentioned.
What are you working on Wellcome Sanger that you find especially interesting?
I would say our ‘DERMATLAS’ Project - a Genomic Atlas of Dermatopathology. This work brings together a group of world-leading pathologists from many different countries to sequence the genomes of rare skin cancers to define drivers and mutational processes. It is a large scale effort to explore tumors that develop in skin. There are more than 70 different cell types in skin. We are looking at how genes are mutated in these cells and how these mutations ultimately contribute to tumor formation.
Related to our work on multiplexed assays of variant effects, or MAVES, is to understand why some individuals are predisposed to developing these conditions. That is, asking the question, “Why some people develop these rare skin cancers more frequently than others?” If we can work out who is at risk, we can push forward things like screening of these individuals and, potentially, decrease their risks of that first outcome. This, we hope, will benefit patient communities around the world.
Learn more about the upcoming MSS 2025 in Barcelona here, including the deadline for “early bird” registration.
