MSS 2025 organizers (left to right) Benedetta Bolognesi, Mafalda Dias, and Jonathan Frazer: 'Moving on from classical mutational scans... to showcasing multiple phenotyping strategies and quantitative modelling based on biophysical or biochemical measurements obtained at scale.'
[Editor’s note: The 8th annual Mutational Scanning Symposium will be held in Barcelona, Spain, May 21-23, at the Barcelona Biomedical Research Park. It will be hosted by the Institute for Bioengineering of Catalunya (IBEC), the Centre for Genomic Regulation (CRG), and the Atlas of Variant Effects (AVE) Alliance. Here, organizers Benedetta Bolognesi of IBEC and Mafalda Dias and Jonathan Frazer of CRG, offer insights into planning for the symposium.]
What are the key themes and topics that will be covered at the symposium?
Benedetta Bolognesi: The topics include, but are not limited to: Computational genetics, Biophysical modelling, Variant interpretation, and Functional genomics.
Mafalda Dias: This is very much related to your question on where do we see the field of mutational scanning evolving. We want this year's symposium to reflect new experimental approaches – assaying multiple phenotypes and biophysical molecular properties – and developments in computational modelling.
Jonathan Frazer: The name of the conference this year is “Mapping and Modelling Variant Effects at Scale” which we chose in part to reflect our excitement about the fact that the interplay between computational models (both deep and “shallow”) and high-throughput experiments is becoming very rich.
What new features or sessions will be introduced this year (opportunities, or new technologies being showcased)?
Bolognesi: I am particularly excited we are moving on from classical mutational scans that I would define as “one gene - one phenotype,” to showcasing multiple phenotyping strategies and quantitative modelling based on biophysical or biochemical measurements obtained at scale. We have also aimed at including some new ingredients in terms of technological approaches, such as genome editing and droplet-based selection assays, as well elements of machine learning in protein design.
Dias: We are particularly excited to showcase some of the latest developments in experimental and computational approaches, while keeping the core ethos of this symposium series – bringing together the whole community from clinical practitioners to academic and industry researchers.
Frazer: I agree with Benedetta that the growing trend of measuring multiple phenotypes is particularly exciting. As a model builder, this is something I have been really looking forward to.
How do you see the field of mutational scanning evolving in the next five years, and what role do you hope the symposium will play in that evolution?
Bolognesi: I hope this meeting will maintain the key role it has played in bridging the community of scientists and clinicians who aim to use deep mutational scanning for clinical variant interpretation to those developing computational approaches who use large mutagenesis datasets for mechanistic modelling and protein design. MSS 2025 will host experts from the academic, clinical, industry and AI communities - a feature, I think, captures the direction in which the field is moving.
There is a lot to learn from the cross-talk between communities, and the symposium has been one of the best stages for this over the years. I guess one of our global goals as the Atlas of Variant Effects community is not just to become able to preventively know if a mutation is pathogenic or not, but also “how” a specific variant is pathogenic. Mechanistic models that make use of deep and combinatorial mutagenesis datasets will become crucial towards this goal.
Barcelona has a thriving crowd when it comes to mutational scanning, functional genomics, and computational genetics. We are very excited to host such a line-up of speakers for MSS 2025 and can't wait for early career scientists from across the globe to join us in a stunning location to discuss science, while looking at the Mediterranean.
Dias: The rapid development of high-throughput technologies allowing for the measurement of different phenotypes at scale will open the door to new modelling avenues which can impact applications from protein and drug design to the clinical practice. Our objective with MSS 2025 is to provide a platform to bridge all these communities.
Frazer: I think it’s becoming increasingly clear that our ability to map genotype to molecular and organismal phenotypes will accelerate dramatically by establishing closer ties between computational modelling and experimental design. I’m hopeful that breakthroughs in this space will come from collaborative efforts between experimental and deep learning groups. The symposium is the perfect place for these collaborations to bud.
Another area where I think we will see substantial transformations in the next few years is in variant annotation for the clinic. Mapping and modelling variant effects at scale and with sufficient accuracy to be of clinical value represent a high bar, but we seem to be getting there. This is an area where community-wide coordinated efforts are especially powerful and the MSS 2025 symposium looks set to play a key role in this.
(For more information, including confirmed speakers, visit the symposium website.)
