Description
This workshop—led by the organizers of the Undiagnosed Hackathon—introduces powerful multiomic approaches that combine long- and short-read sequencing, RNA, and methylation data with clinical insights to help decode complex undiagnosed disease cases. The session begins with a short talk on how the annual hackathon unites expert teams and cutting‑edge tools to solve real rare disease puzzles. Participants then spend hands‑on time with AI‑enhanced tools working in small groups to analyze pre-collected data and solve real cases.
Registrants will need to create accounts for each of the software tools being used. This will take up to 30 minutes to complete prior to the event. Access to these platforms is essential for the hand-on activities included in the workshop.
Individuals living with a longstanding, undiagnosed medical condition are likely to eventually receive diagnosis of a rare disease. Rare and undiagnosed diseases impact approximately 300 million people across the globe. With estimates that 60% of those affected remain undiagnosed, such diseases could affect as many as 600 million individuals world-wide. The complexity of diagnosing individuals with a rare disease is well known and is often termed the ‘diagnostic odyssey’ due to the fact that people living with rare and undiagnosed disease average up to six years to get a diagnosis, if at all.
Integrated, multiomic approaches—long- and short-read genome and exome, RNA, and methylation sequencing—help clarify mechanisms of variants of unknown significance and when combined with phenotypic and clinical data help solve complex undiagnosed cases. Led by the organizers of the Undiagnosed Hackathon, this workshop will provide an overview and hands-on use of several tools available to the human genomics community that aid multiomic analyses and have been used successfully to solve rare and undiagnosed disease cases. Unfortunately, pathways for diagnosis and treatment remain underdeveloped. The Undiagnosed Hackathon (UH) is an innovative collaborative approach aimed at correcting these insufficiencies providing hope and answers for PLWUD.
The workshop will kick off with a 30-minute talk from the Undiagnosed Hackathon organizers about how their annual event brings together multidisciplinary teams and industry-leading tools to solve real cases and help families better understand and seek treatment for their affected loved ones. We invite a multidisciplinary set of participants, including molecular geneticists, data scientists and bioinformaticians, clinicians, genetic counselors, and other health professionals to then spend 4.5 hours of hands‑on time with AI‑enhanced tools working in small groups to analyze pre-collected multiomic data and solve real cases just as a detective would.
We will use state-of-the-art, AI-enhanced tools such as Illumina’s Emedgene, Qiagen’s Franklin, RNAVision and GeneDx’s Fabric GEM. Workshop participants will actively work in small groups to use the data and tools to identify variants of interest from remaining unsolved cases from the Undiagnosed Hackathons. Participants will be required to have access to a laptop with internet access and create accounts for the tools being used.
Learning Objectives: After participating in this workshop, participants will be able to:
- Integrate multiomic workflows with phenotypic and clinical data to solve difficult cases.
- Utilize AI-enhanced short- and long-read genome and exome variant interpretation to speed accurate discovery of variants of interest.
- Analyze RNA‑ and methylation-seq data as additional evidence to resolve variants of unknown significance and splice/non-coding variants.
- Work effectively in groups with experts from difficult fields and backgrounds to successfully address questions and solve problems.
Following an introduction on how 10 cases previous were interrogated with the described tools there will be 2 concurrent opportunities to participate in this workshop:
- Introduction: What tools are applied to a diagnosis and an Undiagnosed Hackathon (UH). Dr. Paul Lasko, McGill University, Dr. Eric Klee and Dr. Cherisse Marcou from the Mayo clinic will review 10 undiagnosed cases that were unsolved after review from an established Undiagnosed Disease Program (UDP). The ‘omic tools that were applied to these cases will be demonstrated in a step-wise process with the addition of new tools that may finally result in a diagnosis.
- Station 1: Learn how to use ‘Omics analytical tools. On hands demonstration of a number of ‘omics tools including EmedGene, Fabric, RNAVision and others by the developers of these tools on a select number of Undiagnosed cases.
- Station 2: New Tools for Diagnosis. Dr. Paul Lasko, Dr. Eric Klee and Dr. Cherisse Marcou will lead a group where new tools will be applied to 10 cases that remain undiagnosed after a UDP and an UH.
While the intent is to be able to move between these 2 stations they are designed for the beginner-to-intermediate and expert diagnostician in the use of informatics, respectively. Please indicate in your registration which of the 2 you are most likely to attend. Appropriate data sets for each station will be made available 2-weeks prior to the workshop.
