Researchers from the Netherlands reported at ESHG that long-read genome sequencing as a first-tier diagnostic test may not substantially increase diagnostic yield versus short-read testing, but it improved interpretation and reduced follow-up testing and overall time to diagnosis. The implementation study compared results from the first six months of long-read sequencing with prior short-read workflows. Tessa de Bitter of Radboud University Medical Center said the team observed a comparable diagnostic yield with slightly enhanced but not yet statistically significant improvements, alongside workflow consolidation and faster results. The program uses Pacific Biosciences technology with automated sample preparation and dedicated sequencing capacity across PacBio Revio systems. The team previously published in the New England Journal of Medicine that long-read sequencing increased conclusive diagnoses by 3% for 832 patients, driven largely by haplotype phasing and detection of novel variants. For rare disease diagnostics, the report strengthens the case that long-read platforms can add practical value by streamlining the clinical diagnostic pipeline.