This rare disease month, we’ve explored the power of telling families’ stories and the impact of adopting HiFi sequencing in real-world settings. Each perspective is a valuable piece of the rare disease community. Behind every dataset is a person searching for clarity and behind every study is a community working to move the field forward.
For our last post of the series, we want to highlight another place where progress is taking shape in the community. Recently, we’ve seen how hackathons are serving as a new and focused way to accelerate answers. These events are inspiring and contagious in spirit, gathering experts from across the world with a shared challenge to roll up their sleeves and dig in together.
What hackathons make possible
So what exactly is a hackathon? Rare disease hackathons are community events that bring together the best of the best. Bioinformaticians, physician scientists, clinical geneticists, and variant analysts come together to hear directly from rare disease families and their care teams. Armed with high-quality genomic data and clinical phenotypes, these teams spend a concentrated window of time working intensively to solve complex, unsolved rare disease cases.
We know that individuals living with undiagnosed disease often endure a diagnostic odyssey that can stretch six years or more. By compressing phenotype review, bioinformatic analysis, and interdisciplinary interpretation into a concentrated window, hackathons aim to shorten that journey.
Antonio Martínez Monseny, Head of the Medical Genetics Unit at SJD Barcelona Children’s Hospital, emphasizes –
“Hackathons compress the full diagnostic cycle into a short, high-focus window. In rare disease, the bottleneck is often not data generation but interpretation and clinical correlation. Bringing medical geneticists, lab geneticists, clinicians, and bioinformaticians into the same room with a shared goal accelerates that process.”
A global movement of the Wilhelm Foundation’s Undiagnosed Hackathons
The Wilhelm Foundation’s 2025 Undiagnosed Hackathon is a great example of one of these community events that was held in collaboration with Mayo Clinic last September. The event brought together 122 collaborators and technical support members from across the globe to examine 29 participant cases representing 18 countries. Clinicians, clinical geneticists, data scientists, molecular biologists, and bioinformaticians worked side by side, guided by detailed phenotypes and the lived expertise of families. These experts banded together armed with genomic and Kinnex full-length RNA sequencing data, and in just 48 hours, identified definitive findings for six participants and promising leads for nine more.
Organizers described the long-read data as instrumental to the overall assessments and shared that the support helped give hope and opportunities to individuals and families living with undiagnosed diseases. Even after the event wrapped, teams continued digging into the data, building on the momentum and sustaining the commitment that had filled the room.
This momentum carried into the new year and across continents, with the 2026 Undiagnosed Hackathon hosted earlier this month at the BRIC-Centre for DNA Fingerprinting and Diagnostics (CDFD) in Hyderabad India, for the country’s first rare disease hackathon. Organized in partnership with the Wilhelm Foundation, Sir Ganga Ram Hospital, AVPN Singapore, and the Society for Indian Academy of Medical Genetics, the event brought together more than 100 experts from 10 countries to work intensively on 25 complex undiagnosed cases. With the inclusion of HiFi long-read WGS data, the teams were able to interrogate the full spectrum of genomic variation from a single comprehensive assay with a more biologically coherent view.
Dr. Usha Dutta, Co-Investigator of CDFD’s Mission Program on Pediatric Rare Genetic Disorders, spoke to what makes this environment so powerful —
“Hackathons create a uniquely enabling environment for exploring and adopting emerging technologies, such as long-read sequencing, in rare disease research by temporarily removing many of the practical constraints that limit routine clinical workflows. In standard diagnostics, workflows are optimized for scalability, cost-efficiency, and turnaround time. In contrast, a hackathon setting encourages scientific curiosity, flexibility, and methodological experimentation.”
The Hyderabad hackathon resulted in explanations for seven cases. In one particularly striking example, a case that was negative by exome sequencing and unresolved by short reads was ultimately explained by a larger structural variant that could only be identified with HiFi long reads. Beyond that single example, the seven resolved cases represent a turning point for the families involved, replacing years of unanswered questions with direction and possibility.
Building networks through the Únicas Hackathon
In another example in Murcia, Spain, more than 100 experts from across Europe and Latin America gathered last October for the first Únicas Hackathon focused on undiagnosed pediatric rare diseases. Over two days, teams analyzed 12 complex cases, some of which had been searching for an explanation for more than a decade. These explanations were found for five participants and one sibling.
Martínez Monseny describes why this model works—
“Hackathons lower the practical and psychological barriers to adopting newer technologies. In routine workflows, decisions are constrained by throughput, cost, turnaround time, and ‘what we’ve always done.’ In a hackathon, the objective is different: maximize insight per case.”
In several cases, HiFi sequencing provided the linchpin for clear and confident findings. It validated findings suggested by other methods and helped definitively rule out structural variants and repeat expansions when those were suspected contributors. This setting gave teams the space to question earlier assumptions and chase down answers with more confidence.
Radboud’s Undiagnosed Hackathon in Nijmegen
At Radboud University Medical Center in Nijmegen, the Undiagnosed Hackathon model has further demonstrated the power of collaborative interpretation. In the 2024 event, interdisciplinary teams evaluated data from 42 undiagnosed families from 19 countries. This event brought together existing data and entirely new datasets, including HiFi long-read genomes.
The outcome included ten definitive diagnostic findings (a 24% solve rate within 48 hours), with additional likely diagnoses identified. Notably, “long-read genomes were most instrumental, validating the importance of complete genomes for clinical variant interpretation.”
Professor Christian Gilissen emphasizes the broader impact –
“Hackathons are amazing events because they bring together all involved parties with individual expertise into one room, which can give rise to completely new insights. They often encourage teams to try methods they wouldn’t normally use in routine workflows and have been tremendously helpful in making individuals familiar with approaches new to rare disease research, including long-read sequencing, by having them actively work with these datasets in a supporting environment where expertise is readily available.”
These events generate tons of valuable data and enable others to use it. PacBio maintains an active commitment to supporting the bioinformatics community through tool development, education, and hands-on collaboration. This means working alongside researchers at these events to analyze HiFi data in real time and sharing learnings on best practices for working with HiFi data. The goal is twofold; to help solve cases in the moment and to build lasting confidence in analyzing HiFi long-read data for rare disease. In many cases, participants carry these insights back to their home institutions, applying what they’ve learned to improve routine variant analysis and interpretation, helping inform downstream clinical insights long after the hackathon ends.
Where collaboration leads next
Rare disease research takes clinicians, scientists, bioinformaticians, technologists, families, and their physicians working in concert. Hackathons show what can happen when that kind of collaboration is coordinated within the community.
The lessons learned in these focused settings can help how we approach unsolved cases at scale and, ultimately, help shorten diagnostic journeys for those searching for answers.
To learn more about how PacBio supports rare disease research, visit https://www.pacb.com/research-focus/human/rare-disease/.