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Updated: Oct 11, 2025

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
The Small Open Reading Frame-Encoded Peptides: Advances in Methodologies and Functional Studies.
Lei Chen1,2, Ying Yang1, Yuanliang Zhang1
1State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, 999077, P. R. China.
Small open reading frames (sORFs) encode functional peptides (SEPs) crucial for health and disease. Recent mass spectrometry advances enable their detection and functional study.
Area of Science:
- Genomics
- Proteomics
- Molecular Biology
Background:
- Small open reading frames (sORFs) were historically dismissed as noncoding or junk DNA.
- Emerging evidence indicates sORFs encode functional polypeptides with significant physiological and pathological roles.
- Detecting sORF-encoded peptides (SEPs) presents considerable technical challenges.
Purpose of the Study:
- To review recent advancements in mass spectrometry-based methodologies for identifying SEPs.
- To summarize the progress in functional studies of SEPs.
- To highlight the importance of sORFs in biological systems.
Main Methods:
- Mass spectrometry-based proteomics for direct detection of SEPs.
- Bioinformatic approaches for sORF identification and validation.
- Functional assays to investigate the roles of SEPs.
Main Results:
- Significant progress has been made in developing sensitive mass spectrometry techniques for SEP identification.
- Novel SEPs have been discovered, revealing their involvement in various biological processes.
- Functional studies are beginning to elucidate the roles of SEPs in both normal physiology and disease states.
Conclusions:
- sORFs represent a rich, under-explored source of functional peptides.
- Advances in mass spectrometry are crucial for unlocking the potential of SEP research.
- Further functional characterization of SEPs is essential for understanding their impact on health and disease.
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