Designing an Assay to Evaluate NBS Results Using Targeted Long-Read Sequencing

Abstract

NBS (NBS) is a routine screening process that identifies selected genetic, metabolic, and endocrine disorders that can affect a newborn’s health. Unfortunately, limitations in the follow-up process can create barriers to confirming screening results. Here, we demonstrate the ability of targeted long-read sequencing (T-LRS) in evaluating NBS results. Using adaptive sampling on the Oxford Nanopore platform on 8 positive control samples from Seattle Children’s Hospital, we computationally targeted more than 500 genes relevant to metabolic and non-metabolic disorders and searched for pathogenic variants using a single data source. We detected all genomic variants identified by prior genetic testing, as well as additional variants not previously identified. T-LRS demonstrates to be an efficient and cost-effective method to evaluate individuals after a positive NBS result.