EphaGen

EphaGen is a novel computational tool for quality control in next-generation sequencing (NGS) datasets for diagnosing Mendelian diseases. It aims to improve NGS performance by providing a single arbiter parameter that estimates the probability of missing any clinically relevant variant from a predefined spectrum within a given NGS dataset. This parameter serves as a measure of diagnostic sensitivity for the dataset.

The tool inputs a single NGS dataset in BAM format and a pre-compiled VCF file containing targeted clinically relevant variants. EphaGen then associates the dataset with the arbiter parameter, which intrinsically estimates the likelihood of missing any variant from the defined spectrum.

Case studies involving BRCA1/2 and CFTR sequencing across 43 blood samples and 504 publicly available NGS datasets demonstrate that EphaGen outperforms conventional bioinformatics metrics such as coverage depth and uniformity. The authors recommend incorporating EphaGen as a quality control step in clinical NGS studies to enhance the reliability and accuracy of variant detection.