Talos: Scaling rare disease diagnosis with automated, iterative genomic reanalysis

Talos is an open-source tool designed for the automated reanalysis of genomic data in rare diseases. It efficiently reexamines stored sequencing data as scientific knowledge evolves, achieving a 90% recovery rate of diagnoses with only 1.3 candidate variants flagged per patient for expert review. Deployed across a cohort of nearly 5,000 undiagnosed patients, Talos yielded 241 new diagnoses, representing a 5.1% increase in diagnostic yield. The average time from new evidence to diagnosis was just 32 days, demonstrating the tool's efficiency in systematic reanalysis.