Standards of NGS Data Sharing and Analysis in Ataxias: Recommendations by the NGS Working Group of the Ataxia Global Initiative
Danique Beijer, Brent L. Fogel, Sergi Beltrán, Matt C. Danzi, Andrea H. Németh, Stephan Züchner, Matthis Synofzik, AGI Ataxia NGS genomics, platforms Working Group, A. D. Adarmes, Saud Alhusaini, Mahmoud Reza Ashrafi, Luís Bataller, Enrico Bertini, Sylvia Boesch, Ronald A.M. Buijsen, Emanuel Cassou, Edwin H.W. Chan, Joana Damásio, Karina Carvalho Donis, Ewelina Elert‐Dobkowska, Liena E. O. Elsayed, Carmen Espinós, Haşmet Hanağası, Morteza Heidari, Wolfgang Nachbauer, Jorge Oliveira, Puneet Opal, Coro Paisán‐Ruiz, Hélène Puccio, Francesco Saccà, Maria Luiza Saraiva Pereira, Thorsten Schmidt, Rebecca Schüle, Giovanni Stévanin, Carlo Wilke, Grace Yoon, Neta Zach, Ginevra Zanni
Abstract
The Ataxia Global Initiative (AGI) is a worldwide multi-stakeholder research platform to systematically enhance trial-readiness in degenerative ataxias. The next-generation sequencing (NGS) working group of the AGI aims to improve methods, platforms, and international standards for ataxia NGS analysis and data sharing, ultimately allowing to increase the number of genetically ataxia patients amenable for natural history and treatment trials. Despite extensive implementation of NGS for ataxia patients in clinical and research settings, the diagnostic gap remains sizeable, as approximately 50% of patients with hereditary ataxia remain genetically undiagnosed. One current shortcoming is the fragmentation of patients and NGS datasets on different analysis platforms and databases around the world. The AGI NGS working group in collaboration with the AGI associated research platforms-CAGC, GENESIS, and RD-Connect GPAP-provides clinicians and scientists access to user-friendly and adaptable interfaces to analyze genome-scale patient data. These platforms also foster collaboration within the ataxia community. These efforts and tools have led to the diagnosis of > 500 ataxia patients and the discovery of > 30 novel ataxia genes. Here, the AGI NGS working group presents their consensus recommendations for NGS data sharing initiatives in the ataxia field, focusing on harmonized NGS variant analysis and standardized clinical and metadata collection, combined with collaborative data and analysis tool sharing across platforms.