SWATH-MS Citrullinated Peptide Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods are inadequate for accurately detecting and quantifying citrullinated proteins and peptides, which are markers for cardiovascular diseases and neurodegenerative diseases, due to the subtle mass shift and charge changes caused by citrullination, leading to challenges in high-throughput analysis.
Innovation Solution
The use of SWATH-MS (Sequential Window Acquisition of all Theoretical Fragment Ion Spectra Mass Spectrometry) technology for data-independent acquisition and targeted data extraction, creating a citrullinated library to improve sensitivity and quantitative accuracy in detecting citrullinated proteins and peptides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional mass spectrometry methods are used to detect citrullinated proteins, then the detection process is simple, but the measurement precision is insufficient due to subtle mass shift and charge changes
Solution Approach 1:
The patent divides the mass spectrometry analysis into sequential windows (e.g., 200-400 m/z, 400-600 m/z, etc.) for data-independent acquisition. Each window captures specific fragment ion spectra, allowing comprehensive coverage of the mass range while maintaining high precision for detecting subtle citrullination-related mass shifts and charge changes.
Solution Approach 2:
The patent performs preliminary data extraction and processing to create a citrullinated protein library before formal analysis. This preliminary action includes generating reference spectra and establishing extraction parameters, which significantly improves subsequent detection precision by providing a robust framework for identifying citrullinated proteins amidst complex biological samples.
2Adaptability or versatility
If data-independent acquisition is used to improve comprehensive detection, then the coverage of citrullinated proteins increases, but the data processing complexity increases
Solution Approach 1:
The patent implements feedback mechanisms in the data processing workflow, where extracted spectra are compared against the citrullinated protein library, and results inform subsequent analysis steps. This feedback loop enables comprehensive detection across multiple windows while systematically managing data complexity through iterative refinement and validation.
Solution Approach 2:
The patent introduces an intermediary citrullinated protein library that acts as a reference framework between raw mass spectrometry data and final identification results. This intermediary structure organizes and pre-processes information, making the comprehensive data from multiple windows more manageable and interpretable without losing detection coverage.
3Measurement precision
If targeted data extraction is used to improve quantitative accuracy, then the sensitivity increases, but the method complexity increases
Solution Approach 1:
The patent applies targeted data extraction with locally optimized parameters for different m/z windows and protein types. Each extraction region uses customized settings (isolation window width, collision energy, etc.) tailored to the specific characteristics of citrullinated peptides in that range, maximizing quantitative accuracy while managing overall method complexity through localized optimization rather than uniform complex processing.
Data Source
AI summary
Provided herein are methods and markers for diagnosing cardiovascular disease and/or neurodegenearative diseases in a subject. The methods include obtaining a biological sample from a subject in need of diagnosis and detecting the amount of a citrullinated protein or a citrullinated peptide in the biological sample obtained from said subject.