A Non-targeted Proteomics Newborn Screening Platform for Genetic Disorders

Abstract

Newborn screening using dried blood spot (DBS) samples has made a substantial contribution to public healthcare by detecting patients with genetic disorders as neonates. Targeted measurements of nucleic acids and metabolites have played major roles in newborn screening to date, while the feasibility of new non-targeted approaches, including genome-wide DNA sequencing, has been explored. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for genetic diseases. DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1106 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with inborn errors of immunity by detecting reduced levels of disease causative proteins and cell-phenotypical alterations. Our results indicate that application of non-targeted quantitative protein profiling of DBS samples can forge a new path in screening for genetic disorders.