Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing

Area of Science:

• Genetics
• Genomics
• Reproductive Medicine

Background:

• Prenatal diagnostic testing is crucial for identifying fetal cytogenomic abnormalities.
• Current standard of care often involves multiple, labor-intensive assays.
• Optical genome mapping (OGM) presents a novel approach for comprehensive prenatal genetic analysis.

Purpose of the Study:

• To evaluate Optical Genome Mapping (OGM) as a potential first-tier prenatal diagnostic test.
• To compare the accuracy and efficiency of OGM against traditional standard of care (SOC) methods.
• To assess the reproducibility and cost-effectiveness of OGM in prenatal diagnostics.

Main Methods:

• OGM was performed on 200 prenatal samples from 123 unique cases previously tested with SOC methods.
• Comparison of OGM results with established diagnostic outcomes from SOC testing.
• Assessment of OGM's accuracy, positive predictive value, and reproducibility across sites, operators, and instruments.

Main Results:

• OGM achieved an overall accuracy of 99.6% compared to SOC methods.
• Demonstrated a 100% positive predictive value and 100% reproducibility.
• Identified all classes of pathogenic cytogenomic aberrations in a single assay.

Conclusions:

• OGM shows significant potential as a first-tier prenatal diagnostic test.
• Its high accuracy, cost-effectiveness, and ability to resolve cytogenomic aberrations in one assay offer advantages over current methods.
• Standardized workflow and high-resolution analysis support OGM's role in improving prenatal diagnosis.