Multiplex assays of variant effects (MAVEs): Approaches, Analysis, and Interpretation

Multiplex assays of variant effects (MAVEs) are a series of high throughput experimental methods used to interrogate the phenotypic or functional effects of thousands of genetic variants in parallel. They have rapidly increased our ability to assess variants of uncertain significance (VUS) where rare or unknown variants may be responsible for pathogenic disease-associated effects. Their recent adoption into clinical diagnostics provides additional evidence for variant interpretation and translation.

This week-long residential course offers participants an opportunity to engage with an international team of MAVE experts, and gain insight into the generation, application, analysis, and interpretation and evaluation of MAVE data. Participants will learn how these assays are performed, how to access available tools and resources, and how utilise various analysis pipelines to determine and interpret variant effects according to the American College of Medical Genetics and Genomics (ACMG) framework.

What will this course cover?

This new addition to our programme will be delivered as a combination of seminars and discussions, interactive tutorials, and hands-on laboratory demonstrations and computer practical sessions which cover:

• Introduction to MAVEs and their applications
• How data is generated and the methods of experimentation
• Open Source tools, databases, and resources
• Quality control and analysis of MAVE data
• Evaluation and assessment of suitability of MAVE outputs
• Translation and interpretation of MAVE data in clinical settings

The course content will be delivered in English.

Who is this course for?

This course is open to postdoctoral scientists, advanced PhD students, clinicians or clinical scientists, interested in genetic variant interpretation and actively engaged in or soon to commence research or utilise MAVE and MAVE datasets in their work from anywhere in the world.

What will you achieve?

After completing this course, you will be able to:

• Discuss the principles behind different MAVE assay technologies and their applications.
• Access and work with publicly available MAVE datasets and resources utilising open-source tools and reproducible, well-documented analysis pipelines
• Implement computational workflows for processing and quality control of MAVE data
• Apply appropriate statistical methods to interpret MAVE data
• Analyse real-world MAVE datasets to gain biological insights into a disease or population of interest by integrating them with other data drawn from population genomics or disease association
• Evaluate the potential of MAVE to enable discoveries in disease gene studies and therapeutic development
• Discuss the challenges and opportunities in leveraging MAVE for more equitable global health applications
• Critically evaluate the strengths and limitations of different MAVE approaches

This course will start at approximately 1pm on Sunday 23 November 2025 and end at 3pm on Friday 28 November 2025.

The programme will include lectures, seminars, demonstrations, and hands-on analysis sessions on the following topics:

• Introduction to MAVE
  • Overview and history of MAVE and how and where it is being currently applied
• Applications of MAVE
  • From research to medicine to industry – how has MAVE been incorporated into what we do
• Data generation and experimental design
  • Saturation mutagenesis
  • Massively parallel reporter assays
  • Different phenotypic readout
• MAVE resources and tools
  • How to access relevant resources and utilise open source tools
• Analysis
  • MAVE data analysis pipelines
  • QC and data evaluation
• Interpretation and clinical translation
  • ACMG standards and guidelines for variant interpretation
  • Real-world scenarios and applications of MAVE

Participants will also complete group projects using existing datasets to consolidate their learning.

Training team

David Adams
Wellcome Sanger Institute

Daniel Jaramillo Calle
Wellcome Sanger Institute

Elizabeth Radford
Cambridge University Hospitals NHS

Alan Rubin
University of Melbourne, Australia

How to Apply

1. Start the application
   • Click on the “Apply” button above to start your application. Please note that places are limited and will be awarded based on merit.
2. Demonstrate the course’s relevance to your project/role
   • Our courses are highly subscribed, so it is essential to clearly show how the skills you will learn in the course will be directly applicable and beneficial to your current role/project and how do you plan to disseminate the knowledge after the course.
   • Preference will be given to applicants who are currently working on related projects or soon will be.
3. Letter of recommendation
   
   • Applications must be supported by a recommendation from a scientific or clinical sponsor (e.g., supervisor, line manager, or head of department). Ensure that your sponsor provides a tailored supporting statement by the application deadline. This statement must be uploaded as a PDF document to the registration system within your application. Applications without a supporting statement will not be considered.
4. Need help?
   • If you encounter any problems with the online application process, please contact us at courses@wellcomeconnectingscience.org for assistance.

Application deadline: 18 August 2025

Travel visas
Citizens of many countries can travel to the UK to attend a course or conference without needing a visa. Please check the UK government website for visitor information: https://www.gov.uk/standard-visitor.

The Home Office and UK Government have recently announced the introduction of an Electronic Travel Authorisation (ETA) process which now applies to all visitors coming to the UK. If you are selected to attend it is your responsibility to secure the correct documentation to travel to the UK. You can find more information by following this link

Confirmed attendees requiring a letter to support a visa application should contact us at courses@wellcomeconnectingscience.org.

*The course fee is subsidised by Wellcome Connecting Science.

Reduced rates are available for those who do not require accommodation, please contact us for more information. Please be aware that the campus is based in a rural location and this option is only suitable for attendees who are already based locally and have access to private transport.

Contact us at courses@wellcomeconnectingscience.org for the commercial rate.

The fee will be requested once acceptance is confirmed.

Bursaries

Limited bursaries, covering up to 50% of the course fee, are awarded based on merit. To apply, complete the bursary section of the online application form, explaining why funding would benefit you.

Applicants will be informed of the outcome, along with their course placement, typically within a month of the application deadline.

Please note that both the applicant and sponsor are required to provide a justification for the bursary as part of the application.

Deadline: 18 August 2025

Additional funding opportunities
Visit our support page for additional financial support currently available and to read our most recent article on breaking down financial barriers.

Extra accommodation
If you wish to book onsite accommodation either side of the course dates, please contact Hinxton Hall Conference Centre directly.

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