Uncovering and overcoming common data sharing challenges in the Rare Disease landscape

25 Jun 2024

Global organisations are working to promote effective data sharing across the rare disease landscape to advance research, clinical innovations, and patient outcomes around the world.

Puzzle pieces coming together against a binary code background

By Tudor Groza and Nicole Vasilevsky, Co-Leads of the GA4GH Rare Disease Community

Hundreds of millions of people are estimated to live with a rare disease. However, each patient undergoes an individual journey from diagnosis to treatment. It may take years for patients to receive an accurate diagnosis. Furthermore, because of the inherent rarity of these diseases, with less than two hundred thousand cases per disease, the great majority do not yet have an associated treatment.

Sharing data in the field of rare diseases is critical for advancing research, clinical innovations, and patient outcomes. The aggregation of rare disease data helps researchers identify genetic markers and disease mechanisms, cultivating a global understanding of the field and paving the way for better diagnostics and treatments. It may also contribute to a broader sense of connection between patients and their families who may otherwise be experiencing their diagnostic and care journeys in isolation.

Global collaboration among researchers, clinicians, and institutions — a key goal of the Global Alliance for Genomics and Health (GA4GH) — can help promote responsible data sharing and accelerate discovery and innovation. It can also empower patients and advocacy groups to contribute to the global effort to raise awareness about the impact rare diseases have on patients’ quality of life.

The GA4GH Rare Disease Community of Interest provides a forum for collaborative knowledge exchange related to rare disease research, data sharing, and implementation of GA4GH standards. The Rare Disease Community hosted a session during the GA4GH April Connect 2024 meeting in Ascona, Switzerland, exploring data sharing use cases emerging from the clinical, translational, research, and patient-driven areas of the rare disease field.

Although the needs of these areas differ, the session highlighted a set of common challenges underpinning them — resulting in a rare disease landscape that has scarce and fragmented data. These challenges include language and communication barriers that inhibit patient access to medical information, in addition to an absence of widely applied community standards to capture and share data.

In this blog post, we provide an overview of the different organisations that presented at April Connect, and how they are working to connect the siloed pieces of the rare disease puzzle and promote effective data sharing.

The Undiagnosed Hackathon

The Wilhelm Foundation supports the Undiagnosed Disease Network International and hosts the Undiagnosed Hackathon — a yearly meeting that attempts to find new ways and collaborations to solve undiagnosed diseases.

Integrating genome sequencing in clinical workups has considerably boosted the diagnostic yield for rare diseases. Despite the impressive strides made possible by genome sequencing, at least fifty percent of patients with a rare disease remain undiagnosed. 

To lower this statistic and improve the level of diagnosis and care for patients with an undiagnosed disease, the Undiagnosed Diseases Network International (UDNI) was established in 2014, co-founded by the Wilhelm Foundation. UDNI is a global consortium of clinical investigators who serve undiagnosed disease patients. Their goals are to develop common protocols for community use, collect and share standardised clinical and laboratory data, and create an integrated and collaborative community to investigate the pathophysiology of newly recognised rare diseases while being inclusive of the patient perspective. 

To facilitate internal data sharing, UDNI uses PhenomeCentral — a repository for clinicians and scientists working in the rare disease community to securely share case records. PhenomeCentral is also a founding member of the Matchmaker Exchange, a GA4GH Driver Project that works to build evidence for novel gene-disease relationships for rare disease.

To further support the needs of undiagnosed patients, the Wilhelm Foundation and UDNI organise an annual Undiagnosed Hackathon. This year, the meeting brought together over 120 participants, covering a wide variety of skills and experiences — clinical, bioinformatics, data science, and more. Participants worked towards providing an answer for 40 undiagnosed families. Notably, this gathering is distinguished by the active participation of families and patients, offering a unique opportunity for real-time data exchange and collaboration.

Sharing wisdom, knowledge, and data for care coordination

The Rare Care Centre (Perth, Australia) delivers a one-of-a-kind, cross-sector model of care, elevates the voices of the nursing community, and contributes to Aboriginal data sharing in Australia.

Living with a rare disease is a complex journey that frequently poses physical, emotional, and psychosocial challenges for patients. To meet the diverse needs of rare disease patients and their families, a coordinated and holistic approach to care is essential. The Clinical Centre of Expertise for Rare and Undiagnosed Diseases (Rare Care Centre) is dedicated to ensuring that children with rare and undiagnosed diseases, along with their families, can live their best possible lives.

In addition to clinical services, the Rare Care Centre’s holistic model of care provides digital solutions, educational initiatives, family support programmes, clinical research infrastructure, and access to global professional networks. Importantly, data contributed by patients and their families help to enhance communication and knowledge exchange. This can also help lead to the development of resources, such as Lyfe Languages, which provides an Indigenous medical language translator to address inequitable health outcomes within Indigenous communities. The Rare Care Centre team is also working to integrate Indigenous elements into GA4GH Phenopackets

Another crucial aspect of rare disease patient care is the support and expertise of nurses. To provide an opportunity for nurses to engage in knowledge sharing and problem solving together, the Rare Care Centre supports the Global Nursing Network for Rare Disease. This online community provides access to a suite of educational resources for upskilling nurses in rare and undiagnosed diseases. A key feature of this network is the translation of information into multiple languages to improve accessibility.

Addressing undiagnosed diseases in Singapore

The team at the Undiagnosed Disease Program (UDP) Singapore provides Mendeliome sequencing to aid in rare disease diagnoses and is conducting population-wide, large-scale sequencing, leading to new newborn screening panels for early disease detection.

Singapore’s Undiagnosed Disease Program (UDP) is leveraging genomic sequencing technology to diagnose more patients, helping to shorten their diagnostic journey. Through the BRIDGES program and SUREKids study, UDP’s work focuses on sequencing children with undiagnosed rare disorders, expediting Mendeliome sequencing for critically ill children in the paediatric intensive care unit (PICU) and neonatal ICU (NICU), and contributing to large-scale, whole-genome sequencing on a population scale. 

Critical insights from UDP’s work contributed to the identification of several recessive disorders with high frequencies in the Singaporean population, broadening the scope of newborn screening recommendations. An example recommendation includes screening newborns for Citrin deficiency, an autosomal recessive inborn error of metabolism, through the use of Asian-inclusive screening panels. One of their top priorities is aligning the resulting phenotype data to the Human Phenotype Ontology and the GA4GH Phenopackets standard.

Another focus area of the UDP Singapore team is gaining a deeper understanding of variants of uncertain significance through the Singapore Rare Disease Models and Mechanisms Network (RDMM). Singapore’s RDMM builds upon the Canadian framework, allowing clinicians to discover new disease genes while allowing scientists to study corresponding genes and pathways in model organisms. Singapore’s RDMM is integrated into a global network, facilitating cross-network queries.

Understanding rare chromosome and gene disorders

Unique maintains a patient registry for rare chromosomal and gene disorders with a focus on the temporal aspect of the conditions via longitudinal phenotyping.

Because patient data has inherently personal identifying information associated with it, there have long been efforts to keep this information confidential, consequently fostering data silos. The UK-based organisation, Unique, is actively working to prevent data silos by responsibly sharing data to advance the diagnosis and treatment of rare chromosomal and gene disorders, while maintaining transparency in data storage, sharing protocols, privacy, and consent management.

Unique maintains a patient registry dedicated to families impacted by rare chromosomal and gene disorders, currently counting over 29,000 members globally. The mission of the organisation encompasses three key objectives: furnishing high-quality, patient-friendly information about the disorders; facilitating connections among and communication between families and clinicians; and providing a forum for peer-to-peer support.

The registry compiles personal information and genetic results such as karyotypes, sequencing data, and detailed phenotype information, in addition to psycho-social insights. A distinguishing factor is the longitudinal nature of the information being captured. This information includes developmental milestones in addition to treatment and therapy history throughout patients’ lifetimes. Data standardisation, particularly adhering to the Human Phenotype Ontology, is currently one of the organisation’s main objectives, to enable seamless exchange of data across systems, institutions, and geographies.

Facilitating direct patient data exchange

MyGene2 enables immediate and public gene and variant data sharing for families of rare disease patients.

Even after genetic sequencing, many individuals may not receive a diagnosis or treatment plan. MyGene2 is a platform that aims to put power and control back into the hands of patients and their families by empowering them to participate directly in data sharing, gene discovery, and research into genotype-phenotype relationships.

The MyGene2 platform encourages families to openly share their clinical findings and genetic data with other families, clinicians, and researchers. Discoveries are promptly shared as citable “match reports” in real-time, fostering direct family involvement in matchmaking and gene discovery efforts.

The platform — part of the MatchMaker Exchange network — hosts public data, accessible via search engines using gene names, variants, and associated phenotypes mapped to Human Phenotype Ontology terms. To connect with other datasets, the team aims to add support for GA4GH Phenopackets and join the GA4GH federated variant-level matching network. Efforts are also underway to increase accessibility by developing family-friendly gene-disease relationship summaries.


The challenges outlined here are among the many critical issues faced by the rare disease field and are key areas of focus for the GA4GH Rare Disease Community. To view the full-length presentations from each initiative, please refer to the April Connect Session recording

The GA4GH Community of Interest offers a unique opportunity to engage with other initiatives around a common goal, actively shape ideas and solutions, and put the fragmented rare disease puzzle pieces together to address the critical needs of the field.

To become a member of the Rare Disease Community and join our mailing list for updates on monthly meetings and events, please contact Yasmeen Kurdi. An upcoming focus area of the Community will be on the creation, utility, and adoption of standards for Artificial Intelligence in the rare disease landscape. We look forward to welcoming more participants and meeting you in person at the GA4GH 12th Plenary in Melbourne, Australia.

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