An open-source tool called Talos demonstrated a scalable path for automated genomic reanalysis in an evaluation of 4,735 unsolved rare disease genomes, reporting 241 diagnoses, with over half linked to newly discovered gene–variant–disease relationships. Developed by Australia’s Centre for Population Genomics in collaboration with Australian Genomics, the Broad Institute and Microsoft Research, Talos aims to address the scalability gap in traditional reanalysis workflows, which often depend on patient- and clinician-driven requests. The software is described as redeployable and customizable across institutions, while requiring manual review for clinically positive calls to maintain specificity. The study referenced publication in Nature Medicine and highlights that Talos focuses on high-confidence disease associations drawn from PanelApp Australia and ClinVar. For clinical programs and diagnostic labs, the work offers a blueprint for integrating continuously updated genomic knowledge into routine casework, potentially shortening time to diagnostic resolution.