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09:04
Selected Reaction Monitoring Mass Spectrometry for Absolute Protein Quantification
Published on: August 17, 2015
Quantitative detection of single amino acid polymorphisms by targeted proteomics
Zhi-Duan Su1, Liang Sun, Dan-Xia Yu
1Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Journal of Molecular Cell Biology
|October 27, 2011
Summary
This study introduces single amino acid polymorphisms (SAPs) as proteome-level variations. Researchers found that different SAPs in individuals are associated with traits like obesity and diabetes.
Area of Science:
- Proteomics
- Genetics
- Human Plasma Analysis
Background:
- Single-nucleotide polymorphisms (SNPs) are known genetic variations, but proteome-level variations in populations are not well understood.
- Amino acid variations arising from SNPs in coding regions, termed single amino acid polymorphisms (SAPs), represent a key area for proteomic investigation.
Purpose of the Study:
- To develop and apply a proteomics pipeline for identifying and quantifying single amino acid polymorphisms (SAPs) in human plasma.
- To investigate the associations of SAPs with common traits such as obesity and diabetes in a population cohort.
Main Methods:
- Utilized a non-targeted and targeted proteomics pipeline to identify and quantify SAP peptides.
- Employed the selected reaction monitoring (SRM) approach to measure absolute concentrations of specific SAP-peptide pairs.
- Analyzed associations between SAPs and traits in 290 Asian individuals.
Main Results:
- Successfully identified and quantified SAP peptides in human plasma.
- Demonstrated that heterozygotes and homozygotes with specific SAPs exhibit differential associations with traits like obesity and diabetes.
- The SRM method enabled the distinct measurement of SAP peptide concentrations in heterozygotes, revealing trait-specific associations.
Conclusions:
- Single amino acid polymorphisms (SAPs) are measurable proteomic variations with population-level significance.
- SAPs, particularly in heterozygous states, show distinct associations with complex human traits, offering new insights into disease etiology.
- This research establishes a foundation for using proteomics to study genetic variation's impact on health outcomes.
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