US 8,935,101 B2Granted

Method and apparatus for correlating precursor and product ions in all-ions fragmentation experiments

AssigneeThermo Finnigan LLC

InventorDavid A. Wright

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Abstract

A method for matching precursor ions to product ions generated in a chromatography—mass spectrometry experiment comprises: choosing a time window defining a region of interest for precursor ion data and product ion data generated by the experiment; constructing a plurality of extracted ion chromatograms (XICs) for the precursor ion data and the product ion data within the region of interest; automatically detecting and characterizing chromatogram peaks within each XIC and automatically generating synthetic analytical fit peaks thereof; discarding a subset of the synthetic analytical peaks which do not satisfy noise reduction rules; performing a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks; and recognizing matches between precursor ions and product ions based on the cross correlation scores.

Claims19

Dependent claims

A method for performing a chromatography—mass spectrometry experiment, comprising:

(a) repeatedly performing, during a time window of the experiment defining a region of interest, the steps of:
(a1) introducing, into a mass spectrometer, a sample of ions generated from one or more chemical compounds eluting from a chromatograph;
(a2) analyzing a first portion of the introduced ions, using a mass analyzer of the mass spectrometer, so as to generate a precursor-ion mass spectrum;
(a3) fragmenting, in a reaction cell of the mass spectrometer, a second portion of the introduced ions, so as to generate product ions;
and
(a4) analyzing the product ions, using the mass analyzer, so as to generate a product ion mass spectrum, wherein plurality of precursor ion mass spectra and plurality of product ion mass spectra resulting from the repeated performing respectively comprise precursor ion data and product ion data;
(b) calculating a plurality of extracted ion chromatograms (XICs) for the precursor ion data and the product ion data within the region of interest;
(c) automatically detecting and characterizing chromatogram peaks within each XIC and automatically generating synthetic analytical fit peaks thereof;
(d) discarding a subset of the synthetic analytical fit peaks which do not satisfy noise reduction rules;
(e) performing a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks;
(f) recognizing matches between precursor ions and product ions based on the cross correlation scores;
and
(g) adjusting the operation of the chromatograph or the mass spectrometer during a subsequent execution of steps (a1) through (a4) during a second, subsequent time window of the experiment, said adjustment based on the automatically recognized matches between precursor ions and product ions.

10 more elements

An apparatus comprising:

a chromatograph for providing a stream of separated chemical substances;
a mass spectrometer fluidically coupled to the chromatograph for generating a plurality of precursor ions from each separated chemical substance and a plurality of product ions resulting from simultaneous fragmentation of each of the precursor ions;
a detector for detecting abundance data for each product ion and each product ion;
and
a programmable electronic processor electrically coupled to the mass spectrometer, the chromatograph and the detector, the programmable processor comprising instructions operable to cause the programmable processor to:
receive the abundance data for each of the product ions and precursor ions detected by the detector during a time window;
automatically detect and characterize chromatogram peaks as a function of time for each of a plurality of mass-to-charge ratio ranges of the abundance data for the product ions and precursor ions;
automatically generate synthetic analytical fit peaks to the detected chromatogram peaks;
automatically discard a subset of the synthetic analytical fit peaks which do not satisfy noise reduction rules;
automatically perform a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks;
and
automatically recognize matches between precursor ions and product ions based on the cross correlation scores.

9 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/970,570Filed 16 Dec 2010
Published: US 2012/0158318 A121 Jun 2012
Granted: 13 Jan 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

G01N 30/8675
Signal analysis: evaluation, i.e. decoding of the signal into analytical information
B01D 59/44
Separation of different isotopes of the same chemical element: separation by mass spectrography
G01N 15/02
Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials: investigating particle…
G01N 30/72
Detectors specially adapted therefor: mass spectrometers