Data independent acquisition of product ion spectra and reference spectra library matching
Inventors
Bonner, Ronald F. • Tate, Stephen A. • AEBERSOLD, RUDOLF • Navarro ALvarez, Pedro Jose • Rinner, Oliver • Reiter, Lukas • Gillet, Ludovic
Assignees
Eidgenoessische Technische Hochschule Zurich ETHZ • Biognosys AG • DH Technologies Development Pte Ltd
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9343279-B2
Publication Date
2016-05-17
Expiration Date
Abstract
Systems and methods are disclosed for identifying detectable compounds of a sample. Sample product ion spectra are received for each mass selection window of precursor mass selection windows for each time step. The received sample product ion spectra are searched for the presence of known compounds of interest with known product ion spectra by retrieving a known product ion spectrum from a library, retrieving the sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time for the retrieved sample product ion spectra, calculating a score for the product ion traces and the retrieved sample product ion spectra that represents how well the retrieved sample product ion spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.
Core Innovation
The invention identifies detectable compounds of a sample by receiving sample product ion spectra for each mass selection window of a plurality of precursor mass selection windows for each time step of a plurality of time steps. The sample product ion spectra are produced by separating detectable compounds in a sample over time and, at each time step, analyzing the detectable compounds by performing a plurality of product ion scans for precursor mass selection windows selected across a mass range using a tandem mass spectrometer.
A processor or measurement module searches the received sample product ion spectra for the presence of one or more known compounds with known product ion spectra. The searching includes retrieving a known product ion spectrum from a library, retrieving the sample product ion spectra corresponding to a precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time for the retrieved sample product ion spectra, calculating a score representing how well the retrieved sample product ion spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.
The approach further identifies modified forms of known compounds by using retrieved sample product ion spectra, locating characteristic modified ions in one or more isolation windows, extracting a spectrum for modification characterization, and determining the type and location of the modification by comparison to expected modification masses.
Claims Coverage
The independent claims cover three embodiments: a system, a method, and a computer program product. Across these independent claims, the core inventive features are time-resolved sample product ion spectra across multiple precursor mass selection windows, searching against known product ion spectra from a library by generating time-based product ion traces, scoring the match to confirm precursor ion identity, and extending to modified forms and modification type and location characterization.
System for identifying detectable compounds using time-resolved precursor window product ion spectra and library scoring
A processor receives sample product ion spectra for each mass selection window of a plurality of precursor mass selection windows for each time step, the sample product ion spectra being produced by separating detectable compounds in a sample over time and performing a plurality of product ion scans for precursor mass selection windows selected across a mass range using a tandem mass spectrometer, and the processor searches the received spectra for one or more known compounds by retrieving a known product ion spectrum from a library, retrieving sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time, calculating a score representing how well the retrieved spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.
Method for identifying detectable compounds using time-resolved precursor window product ion spectra and library scoring
Receiving sample product ion spectra for each mass selection window of a plurality of precursor mass selection windows for each time step using a processor, the spectra being produced by separating detectable compounds over time and, at each time step, analyzing the detectable compounds by performing a plurality of product ion scans for precursor mass selection windows selected across a mass range using a tandem mass spectrometer; and searching the received spectra for the presence of one or more known compounds of interest with known product ion spectra by retrieving a known product ion spectrum from a library, retrieving sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time, calculating a score representing how well the retrieved spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.
Computer program product for identifying detectable compounds using measurement module time-resolved precursor window product ion spectra and library scoring
A computer program product on a tangible non-transitory computer-readable storage medium includes instructions executed on a processor to provide a system with one or more distinct software modules comprising a measurement module, to receive sample product ion spectra for each mass selection window of a plurality of precursor mass selection windows for each time step using the measurement module, and to search the received product ion spectra for one or more known compounds with known product ion spectra by retrieving a known product ion spectrum from a library, retrieving sample product ion spectra corresponding to the precursor mass selection window expected to contain a precursor ion corresponding to the known product ion spectrum, generating product ion traces in time, calculating a score representing how well the retrieved spectra and the known product ion spectrum match, and confirming the identity of a precursor ion using the score.
Across the independent claims, the core inventive concept is a workflow that receives time-resolved sample product ion spectra across multiple precursor mass selection windows, retrieves known product ion spectra from a library, generates time-based product ion traces from the expected isolation window content, computes a match score to confirm precursor ion identity, and supports modified forms and modification type and location characterization.
Stated Advantages
Provides improved confidence via full MS2 matching on wide windows.
Avoids preliminary transition design compared with SRM.
Enables dynamic re-analysis from stored data.
Supports iterative discovery and refinement.
Documented Applications
Matching and identifying detectable compounds by mining time-resolved MS2 product ion spectra maps and comparing to a reference/product ion library, including identification of modified forms and characterization of modification type and location.
Interested in licensing this patent?