SEPepQuant Enhances the Detection of Possible Isoform Regulations in Shotgun Proteomics

Authors

Yongchao Dou
Yuejia Liu
Xinpei Yi
Lindsey K Olsen
Hongwen Zhu
Qiang Gao
Hu Zhou
Bing Zhang

Publication Date

9-19-2023

Journal

Nature Communications

DOI

10.1038/s41467-023-41558-2

PMID

37726316

PMCID

PMC10509223

PubMedCentral® Posted Date

9-19-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Proteomics, Protein Isoforms, Biomedical Research, Carcinoma, Hepatocellular, Liver Neoplasms

Abstract

Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key limitations of existing methods, providing more comprehensive isoform-level characterization, identifying hundreds of isoform-level regulation events, and facilitating streamlined cross-study comparisons. Our analysis provides solid evidence to support a widespread role of protein isoform regulation in normal and disease processes, and SEPepQuant has broad applications to biological and translational research.