3 Results
3.1 Selection of sequencing
methods for neonatal screening
To select the appropriate detection method, we firstly compared
different sequencing methods for NBS used in the previously published
studies (Table 1). In the beginning, scientists conducted neonatal
screening trials by using whole exome sequencing (WES) or whole genome
sequencing (WGS), including WGS for STATseq project16,
WES for BabySeq project17, NBSeq
project27, and North Carolina Newborn Exome Sequencing
for Universal Screening (NC NEXUS) project18. These
studies implied sequencing may screen out inborn errors before the
disease onset and WGS/WES is operationally feasible in neonatal
screening28-32. However, WGS/WES analysis produces
lots of VUS, shows the higher cost and longer turn-around time (TAT).
Consequently, scientists explored the application of targeted NGS panels
that only analyzed a subset of gene loci in NBS. Notably, studies
suggested that targeted sequencing has more advantages over WGS/WES as
the operation of data analysis/follow-up is more feasible and easier,
with lower cost, shorter TAT, and easier interpretation33,34. Additionally, there is little difference in
positive rate between targeted NGS and WGS/WES35.
Therefore, we choose targeted
sequencing in our study.