Modified Compound Identification via XIC Peak Grouping

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Solution Overview

Problem

In complex mixtures, traditional information-dependent acquisition (IDA) methods struggle to detect and identify modified forms of compounds due to product ion spectra containing ions from multiple precursor ions, making it difficult to compare spectra to known compounds.

Innovation Solution

A system and method that utilize a processor to analyze product ion spectra from tandem mass spectrometry data, generating extracted ion chromatograms, grouping peaks by retention time, calculating m/z differences, and counting occurrences to detect modified forms by identifying peaks with excessive m/z difference values, thereby distinguishing modified product ions from known compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional IDA method is used to detect modified forms of compounds, then the method is simple and flexible, but in complex mixtures product ion spectra contain ions from multiple precursor ions making it difficult to compare spectra to known compounds

Engineering Contradiction:
Improvespectral matching accuracyVSAvoiddata processing complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the complex product ion spectrum into multiple extracted ion chromatograms (XICs), each corresponding to a specific precursor ion. By separating the spectrum based on precursor ion masses and their associated product ion patterns, the method isolates individual compound signals from the complex mixture, enabling accurate spectral matching without contamination from other precursor ions.

Inventive Principle:
Principle #1Segmentation

2Reliability

If product ion scans are performed for multiple precursor mass selection windows across the mass range, then more modified forms can be detected, but the data processing and analysis becomes more complex

Engineering Contradiction:
Improvedetection reliability of modified formsVSAvoiddata processing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts relevant information from the complex tandem mass spectrometry data by generating extracted ion chromatograms (XICs) for specific product ions. This extraction process isolates the signals of interest from the overwhelming background data, allowing reliable detection of modified forms while simplifying subsequent analysis through focused examination of specific ion patterns.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent transitions from analyzing two-dimensional mass spectra to utilizing three-dimensional extracted ion chromatograms that incorporate retention time as an additional dimension. This dimensional expansion allows the method to distinguish between co-eluting compounds and confirm modified forms through consistent retention time patterns across multiple product ion scans.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If traditional spectral comparison methods are used, then the analysis is straightforward, but modified forms cannot be reliably identified when product ions from multiple precursors are present

Engineering Contradiction:
Improveidentification accuracyVSAvoidspectral analysis difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent performs preliminary grouping of product ion scans by precursor ion before conducting spectral comparison. By organizing the data structure in advance according to precursor ion identities and generating XICs beforehand, the method prepares the data in a format that facilitates accurate modified form identification while reducing the complexity of subsequent spectral analysis.

Inventive Principle:
Principle #10Preliminary action

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 detects modified forms of compounds in complex mixtures by systematically analyzing product ion spectra, improving the accuracy and reliability of identifying modified compounds through the use of extracted ion chromatogram peak profiles and m/z difference analysis.

Implementation Method 1

analyzing the known compounds by performing a plurality of product ion scans for a plurality of precursor mass selection windows selected across a mass range of the sample using a tandem mass spectrometer

Methodology Applied
Scientific EffectTandem mass spectrometry:

Implementation Method 2

separating known compounds from a sample over time using a separation device

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3218703B1Determining the identity of modified compounds
Publication Date: 2019.06.26 DH TECH DEVMENT PTE
  • EP3218703B1 patent drawingFigure 1
  • EP3218703B1 patent drawingFigure 2
  • EP3218703B1 patent drawingFigure 3

AI summary

Sample product ion spectra are obtained using a data independent acquisition method. Known m/z values of product ions of a known compound are retrieved. Product ion XICs are generated from the sample product ion spectra. XIC peaks of the generated product ion XICs are grouped by retention time. An XIC peak group is selected. An m/z peak list is created for the XIC peak group by obtaining each monoisotopic peak in each spectrum of the selected XIC peak group. Values are removed from the m/z peak list that match the known m/z values. For each value in the m/z peak list, m/z difference values from the known m/z values are calculated. The m/z difference values are grouped and the number of m/z difference values in each group is counted. If a count of an m/z difference value group exceeds a predetermined count, a modified form is detected.