Exploration of Semiconductor Chip-Based Single-Molecule Protein Sequencing for Identification of Hemoglobin Variants

Identification of hemoglobin (Hb)
variants is of significant value
in the clinical diagnosis of hemoglobinopathies. Conventional methods
used to identify Hb variants in clinical laboratories can narrow down
the range of candidates for a Hb variant sample but are unable to
pinpoint the exact Hb variant. In this study, Next-Generation Protein
Sequencing (NGPS), a semiconductor chip-based single-molecule protein
sequencing (SMPS) technology, was explored as a novel method to identify
Hb variants. Two heterozygous Hb variant samples underwent NGPS analysis.
Proteotypic peptides corresponding to Hb variants were successfully
detected, enabling the identification of the samples as Hb Handsworth
(Hb α-Handsworth subunit G18R) and Hb G-Accra (Hb β-G-Accra
subunit D73N). The NGPS method has been demonstrated as a potential
tool to identify Hb variants. Although there are still limitations
to overcome for the wide adoption of NGPS, this exploration supports
the potential use of NGPS and other SMPS technologies in clinical
applications.