Talos: Scaling rare disease diagnosis with automated, iterative genomic reanalysis
AI Summary: Talos is an open-source tool designed for the automated reanalysis of genomic data in rare diseases, enabling the efficient identification of actionable variants as scientific knowledge evolves. In a validation study involving nearly 1,100 patients, Talos achieved a 90% recovery rate of relevant diagnoses while maintaining a low false-positive rate of 1.3 candidate variants per patient for expert review. Deployed in a cohort of almost 5,000 undiagnosed patients, it resulted in 241 new diagnoses, representing a 5.1% increase in diagnostic yield, with an average turnaround of 32 days from the emergence of new evidence to diagnosis. Talos demonstrates that systematic, iterative reanalysis can be conducted sustainably, requiring analysts to review only one new variant per 200 patients on a monthly basis.