Precision medicine's inevitable trajectory toward rare-disease-sized cohorts: implications for machine learning and...

Although precision medicine redefines health care by tailoring treatments to highly specific patient subgroups, the rise of rare-disease-sized cohorts (RDSCs) presents a formidable challenge. RDSCs are the smaller fragmented datasets induced by the precision medicine paradigm; they strain traditional deep learning and machine learning approaches, which typically thrive on large-scale data. In this Viewpoint, we explore the growing tension between the promise of personalised care and the limitations of current data infrastructure and associated algorithmic approaches, drawing lessons from rare disease research. We highlight the need for new methods that can handle the complexities of small, high-dimensional, and heterogeneous datasets. Importantly, although technical innovation is essential, systemic changes in biobanking, data standardisation, and cross-institutional collaboration are equally vital. Without investment in data collection, usage, and governance frameworks, the full potential of precision medicine will remain inaccessible. This Viewpoint attempts to offer a comprehensive roadmap for researchers, clinicians, and policy makers committed to advancing precision medicine in an era where "n=1" may become the new normal.