Post-Translational Modification Detection via Depth-First Search
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current database search tools in proteomics face challenges in identifying post-translational modifications (PTMs) due to reliance on prior knowledge and limited flexibility, with closed searches being accurate but restrictive and open searches being flexible but computationally intensive, and often failing to account for combinations of PTMs.
Innovation Solution
A method and system that automatically detect PTMs by generating and matching post-translational modification combinations using a depth-first search algorithm, allowing for user-defined modifications and validating results across both closed and open search strategies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If closed search strategy is used with tight peptide precursor mass tolerance, then peptide sequence identification accuracy is improved, but the search space is restricted and requires prior knowledge of PTMs
Solution Approach 1:
The patent segments the search process into two distinct phases: closed search for accurate peptide sequence identification with tight mass tolerance, and open search for flexible PTM detection with wide mass tolerance. This segmentation allows each phase to optimize for its specific goal without compromising the other.
Solution Approach 2:
The patent performs preliminary closed search to identify peptide sequences before conducting the open search for PTM detection. This preliminary action establishes a foundation of accurate peptide identification that guides the subsequent PTM analysis, improving overall efficiency and accuracy.
2Adaptability or versatility
If open search strategy is used with wide precursor mass tolerance, then flexibility in PTM detection is improved, but search space dramatically increases and computational complexity rises
Solution Approach 1:
The patent divides the computational workload into two separate search engines with different tolerance settings. The closed search handles accurate peptide identification with minimal computational overhead, while the open search focuses specifically on PTM detection with wider tolerance, reducing the overall computational complexity compared to a single comprehensive open search.
Solution Approach 2:
By performing closed search first to establish accurate peptide sequences, the patent creates a constrained foundation that reduces the search space for the subsequent open search. This preliminary action significantly reduces the computational complexity of the open search phase by eliminating the need to search for both peptide sequences and modifications simultaneously.
3Adaptability or versatility
If multiple PTM combinations are considered, then detection of unanticipated PTMs is improved, but false discovery rate increases
Solution Approach 1:
The patent segments PTM analysis into individual modification detection rather than evaluating all possible combinations simultaneously. Each PTM is detected and validated independently through the two-stage search process, reducing the combinatorial explosion that leads to false discoveries while maintaining the ability to detect multiple different PTMs across the proteome.
Data Source
AI summary
Provided are a method and a system for automatic detection of post-translational modifications (PTMs) detection, where a depth-first search (DFS) algorithm is utilized to generate all post-translational modification combinations and respective masses thereof based on all PTMs associated with compound-spectrum matches of a biological compound, such that a mass shift of a compound-spectrum match of the biological compound generated by search engines with the open search strategy can then be processed by the system and the method provided herein. Therefore, users can validate the search results from the open search via the same search engines with closed strategy for precise identification and discovery of potential unanticipated modifications of the biological compound. Also provided is a computer readable medium with executable instructions stored thereon to perform the method of the present disclosure.