Microsoft Research· Research / Phi

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

Talos is an open-source tool for automated, iterative reanalysis of genomic data in rare disease. It efficiently re-examines stored sequencing data as scientific knowledge evolves and flags variants with newly actionable evidence. Talos is tuned for a low false-positive rate: across a validation set of nearly 1,100 patients, it recovered 90% of in-scope diagnoses while flagging only 1.3 candidate variants per patient for expert review. This is essential to making reanalysis sustainable at scale. Deployed across a prospective cohort of almost 5,000 undiagnosed patients, Talos delivered 241 new diagnoses (5.1% additional yield). An average of only 32 days passed between supporting evidence becoming public and the resultant diagnosis. On monthly iterative cycles, analysts only needed to review one new variant per 200 patients, demonstrating that frequent, systematic reanalysis can be run sustainably. Why genome reanalysis matters Genomic testing has transformed the diagnosis of rare disease, but even with this advancement, more than half of patients remain undiagnosed after their first test. This is because our knowledge of the genome is still incomplete. …

Announced

24 Jun 2026 14:00 UTC