This paper describes a system for the differential diagnosis of ~3,500 genetic disorders in newborns in just 50 hours using whole-genome sequencing (WGS). The rapid turnaround was achieved by decreasing the length of the WGS process and automating the bioinformatic analysis of results. The authors demonstrated the use of this system in a neonatal intensive care unit by providing prospective molecular diagnoses. Crucial time savings could be made using this system in the treatment of newborns with severe genetic conditions.