The rapid development of therapies for severe rare genetic conditions highlights the need to bring first-tier genetic testing into newborn screening (NBS) programs. To address this, a workflow was created to screen newborns for 165 treatable pediatric disorders by deep sequencing regions of interest across 405 genes. Launched in September 2022, the BabyDetect pilot project took place in the Liège area, Belgium. More than 6,000 families were informed about the study, and over 90% consented to participate.

This Trinity Freestyle Fast Hybridization protocol details the steps for performing target enrichment and sequencing on Twist indexed libraries generated with the Twist UDI Primers for Trinity Freestyle. The Twist for Element, Trinity Freestyle Fast Hybridization Kit enables rapid enrichment of libraries generated from Twist's most commonly used library preparation kits, such as Enzymatic Fragmentation 2.0 and FlexPrep UHT kits. The resulting enriched DNA library can be sequenced on Element next-generation sequencing (NGS) systems using the Trinity Freestyle sequencing workflow. This protocol should only be performed with the reagents specified or their equivalents.