Peptide Assignment via Target Sequence Database
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Solution Overview
Problem
Conventional peptide assignment methods struggle to determine the sequences of endogenous peptides produced in vivo with high sensitivity due to increased search space and complex product ion generation patterns, making it difficult to analyze peptides with low production amounts and diverse amino acid distributions.
Innovation Solution
A peptide assignment method and system that create a target peptide sequence database based on known endogenous peptides and their precursor proteins, using mass spectrometry to identify peptide sequences with reduced search space and enhanced sensitivity, specifically by generating target peptide sequences with partial sequences in common, thereby improving detection and analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional peptide assignment methods are used to analyze endogenous peptides, then the analysis can be performed with standard procedures, but the search space increases significantly and sensitivity decreases
Solution Approach 1:
The invention segments the search space by dividing endogenous peptides into two categories: those with known sequences and those with unknown sequences. For known peptides, direct sequence matching is performed. For unknown peptides, the system generates candidate sequences by introducing possible modifications and cleavage patterns to known sequences, then searches only within this reduced candidate space rather than all possible peptide sequences.
Solution Approach 2:
The system performs preliminary actions by pre-generating candidate peptide sequences based on known endogenous peptide sequences and their precursor proteins. This includes pre-calculating possible modifications, cleavage patterns, and variant sequences before the actual mass spectrometry analysis, thereby reducing the search space during the actual peptide assignment process.
2Measurement precision
If proteins are fragmented into peptides using proteases to improve ionization and sensitivity, then analytical sensitivity is improved, but the search space increases when analyzing endogenous peptides with unknown cleavage sites
Solution Approach 1:
The invention applies local quality by treating different regions of the peptide search space differently. For regions corresponding to known endogenous peptide sequences, the system applies strict matching criteria. For regions involving unknown cleavage sites or modifications, the system generates localized candidate variants around the known sequences rather than searching the entire peptide space, thereby maintaining sensitivity while controlling search space expansion.
3Adaptability or versatility
If database search is performed assuming cleaved peptides produced by processing at every site, then all possible endogenous peptides can be searched, but search time increases and identification sensitivity decreases
Solution Approach 1:
The system applies partial action by performing exhaustive searching only for known endogenous peptide sequences and their immediate variants, rather than performing exhaustive searches for all possible peptide sequences. This selective approach provides sufficient coverage for endogenous peptide identification while significantly reducing search time compared to complete exhaustive searching.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively reduces the search space and increases the sensitivity of peptide sequence determination, allowing for more accurate identification of endogenous peptides with high sensitivity, even when conventional methods fail, by using a target peptide sequence database and mass spectrometry to analyze peptide samples.
Implementation Method 1
a mass spectrometry step; In the mass spectrometry step, mass spectrometry is performed on a peptide sample
Data Source
AI summary
Based on an endogenous peptide whose peptide sequence is known among endogenous peptides produced in vivo and on a full-length sequence of a precursor protein of the endogenous peptide, a database creation unit 11 generates a peptide sequence as a target peptide sequence, the peptide sequence containing one or more residues of a partial sequence of the endogenous peptide, thereby creating a target peptide sequence database 111 including a plurality of the target peptide sequences. The mass spectrometry unit 12 performs mass spectrometry on a peptide sample. A peptide assignment unit 14 determines a peptide sequence of an endogenous peptide contained in the peptide sample based on the plurality of target peptide sequences generated by the database creation unit 11 and on a mass spectrum obtained by the mass spectrometry unit 12.