genetic mysteries

PNRI’s Inaugural Rare Disease Hackathon: Uniting Experts to Solve Genetic Mysteries

A Collaborative Effort to Decode Genetic Puzzles

From May 24-26, PNRI hosted its first-ever Rare Disease Hackathon. For three dynamic days, participants immersed themselves in the world of rare diseases. Their mission: uncover disease-causing genetic variants in molecularly unresolved rare disease families. 

For this international team, PNRI’s hackathon offered dedicated time to dive deeper into the data and gave attendees the opportunity to learn and apply new genetic analysis methods.
Most of the samples the hackathon team analyzed were collected from patients a decade ago and recently sequenced using genome sequencing methodology. Many of those affected individuals are now school-aged children with conditions like microcephaly, immunodeficiency disorders, and neurodevelopmental disorders. Having an undiagnosed condition poses significant challenges to access effective medical care for these and other patients since many treatments rely on understanding the specific genetic or molecular basis of a condition. Without a diagnosis, targeted treatments are not accessible. 

“Scientific meetings like this one are crucial because they bring together diverse expertise and foster an environment of intense collaboration and innovation. They allow us to rapidly address complex challenges in rare disease research, ultimately accelerating our understanding and discovery of pathogenic DNA variants.”

Cláudia Carvalho, PhD
Organizer of PNRI Hackathon

Dr. Anna Lindstrand: A Long-Standing Collaboration 

Hackathon co-lead Anna Lindstrand, MD, PhD, who leads the Rare Disease Research group at Sweden’s Karolinska Institutet and Clinical Genetics and the clinical diagnostic laboratory at Karolinska University Hospital has been collaborating with Dr. Carvalho for a decade when both were postdoctoral fellows in different research groups. 

The hackathon was a culmination of Dr. Lindstrand’s month-long visit to work in person with Dr. Carvalho in Seattle that allowed them to dive deep into their joint research on genetic structural variants. Dr. Lindstrand organized a similar hackathon in 2023 that gathered 100 scientists who resolved the molecular diagnoses for four out of ten patients with undiagnosed rare diseases. 

“Precision medicine starts with precision diagnostics. Without knowing the cause of the disease, patients cannot be offered therapeutics, included in clinical trials, or provided with accurate carrier screening or prenatal diagnostics.”

Anna Lindstrand, MD, PhD
Co-Leader of PNRI Hackathon

Gathering Experts 

This weekend was the first hackathon for Jennifer Posey, MD, PhD, who leads the Baylor College of Medicine Genomic Research to Elucidate the Genetics of Rare Disease (BCM-GREGoR) research program.

The hackathon’s focused environment allowed Dr. Posey to dedicate two full days to analyzing data, collaborate closely with experts from other institutions, and gain hands-on experience with advanced tools. Dr. Posey is excited to bring back new discoveries made during the hackathon to the full GREGoR consortium.

“Providing answers about rare conditions is incredibly important for patients and their medical care teams. It helps with managing their care, family planning for the next generation, and opens the possibility for precision therapeutics. Knowing the molecular lesion allows for targeted treatments, paving the way for current and future medical advancements.”

Jennifer Posey, MD, PhD
Hackathon Participant

Haowei Du, PhD, a genetics researcher in the Lupski Lab at Baylor College of Medicine, saw the hackathon as a unique opportunity to learn from experts and network with peers. “This hackathon is well-prepared and focused, allowing us to accomplish more in a short period. A focused approach like this leads to greater productivity.”

Cliff Lun, a bioinformatician in PNRI’s Carvalho Lab who helped prepare and analyze the data said, “The hackathon was a fantastic learning experience, allowing me to refine my data preprocessing skills and gain new insights from various analytical approaches. Collaborating with other professionals and contributing to the event’s conceptualization was truly rewarding.”  

Sebastian Ochoa Gonzalez, MD, a clinical researcher at Texas Children’s and Baylor College of Medicine whose work  focuses on inborn errors of immunity aimed to use modern genetic analysis tools to reanalyze data from 39 undiagnosed families. Although finding definitive answers within the hackathon’s timeframe was ambitious, Sebastian hopes to generate hypotheses and leads for further research, ultimately aiming to develop targeted therapies for affected children worldwide. “Finding strong leads linking novel genes or hidden mutations in known genes to a patient’s disease is the most realistic outcome. These leads provide direction for future research.”

A Promising Future for Rare Disease Research 

The PNRI Rare Disease Hackathon was a resounding success, fostering international collaboration, and identifying important genetic variants that cause rare diseases. The hackathon team’s three-day analysis also revealed more variants to explore further. The work from this weekend will create significant strides in rare disease research—and can lead to life-saving treatments. All who participated are eager to continue their collaborative efforts to solve some of the most challenging genetic mysteries.

To learn more about rare disease research at PNRI, visit:

To learn about the collaboration between Drs. Lindstrand and Carvalho, watch the video below.