Data independent acquisition of product ion spectra and reference spectra library matching

Patent metadata

Field	Value
Publication number	US-9343278-B2
Application number	US-201514741948-A
Country	US
Kind code	B2
Filing date	Jun 17, 2015
Priority date	Sep 15, 2010
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Systems and methods are disclosed for quantitating detectable compounds of a sample. Sample product ion spectra are received for each mass selection window 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 the known product ion spectra 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 spectra, generating product ion traces in time for the sample product ion spectra for the known product ion spectra, calculating a score for the product ion traces and product ion spectra that represents how well known product ions and sample product ions match, and calculating a quantitative value for the known compound from the product ion traces when the score exceeds a threshold value.

First claim

What is claimed is:

1. A system for quantitating detectable compounds of a sample, comprising:
a processor that
receives 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, wherein 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 a plurality of precursor mass selection windows selected across a mass range of the sample using a tandem mass spectrometer, wherein each mass selection window of the plurality of mass selection windows has a width greater than 10 amu; and
searches the received product ion spectra for the presence of one or more known compounds with known product ion spectra by:
a) retrieving the known product ion spectra from a library,
b) 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 spectra,
c) generating product ion traces in time for the sample product ion spectra for one or more of the known product ion spectra,
d) calculating a score for the product ion traces and product ion spectra that represents how well known product ions of the known product ion spectra and sample product ions of the sample product ion spectra match, and
e) calculating a quantitative value for a known compound from the product ion traces when the score exceeds a threshold value.

2. The system of claim 1 , wherein the known compounds comprise one or more of peptides, proteins, complete proteomes, endogenous metabolites, lipids, carbohydrates, or combinations thereof.

3. The system of claim 1 , wherein the known compounds comprise one or more compounds of pharmaceutical, environmental, forensic, or industrial importance.

4. The system of claim 1 , wherein the known product ion spectra are determined from authentic standards of the known compounds, from an analysis of samples containing the compounds or from existing spectral libraries.

5. The system of claim 1 , wherein the processor further uses one or more matching sample product ions from step d) to identify a modified form of one or more compounds of the known compounds.

6. The system of claim 5 wherein the processor compares the matching sample ions to masses predicted from known product ions and a modification to characterize a type and location of the modification.

7. The system of claim 5 , wherein the processor further extracts a spectrum of the identified modified form from the sample product ion spectra in order to characterize a type and location of the modification in the identified modified form.

8. A method for quantitating detectable compounds of a sample, comprising:
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 using a processor, wherein 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 a plurality of precursor mass selection windows selected across a mass range of the sample using a tandem mass spectrometer, wherein each mass selection window of the plurality of mass selection windows has a width greater than 10 amu; and
searching the received sample product ion spectra for the presence of one or more known compounds of interest with known product ion spectra using the processor by:
a) retrieving the known product ion spectra from a library,
b) 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 spectra,
c) generating product ion traces in time for the sample product ion spectra for one or more of the known product ion spectra,
d) calculating a score for the product ion traces and product ion spectra that represents how well known product ions of the known product ion spectra and sample product ions of the sample product ion spectra match, and
e) calculating a quantitative value for the known compound from the product ion traces when the score exceeds a threshold value.

9. The method of claim 8 , wherein the known compounds comprise one or more of peptides, proteins, complete proteomes, endogenous metabolites, lipids, carbohydrates, or combinations thereof.

10. The method of claim 8 , wherein the known compounds comprise one or more compounds of pharmaceutical, environmental, forensic, or industrial importance.

11. The method of claim 8 , wherein the known product ion spectra are determined from authentic standards of the known compounds, from an analysis of samples containing the compounds or from existing spectral libraries.

12. The method of claim 8 , further comprising using one or more matching sample product ions from step d) to identify a modified form of one or more compounds of the known compounds using the processor.

13. The method of claim 12 , further comprising comparing the matching sample ions to masses predicted from known product ions and a modification to characterize a type and location of the modification using the processor.

14. The method of claim 12 , further comprising extracting a spectrum of the identified modified form from the sample product ion spectra in order to characterize a type and location of the modification in the identified modified form using the processor.

15. A computer program product, comprising a tangible non-transitory computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for quantitating detectable compounds of a sample, the method comprising:
providing a system, wherein the system comprises one or more distinct software modules, and wherein the distinct software modules comprise a measurement module; and 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 using the measurement module, wherein 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 a plurality of precursor mass selection windows selected across a mass range of the sample using a tandem mass spectrometer, wherein each mass selection window of the plurality of mass selection windows has a width greater than 10 amu; and
searching the received product ion spectra for the presence of one or more known compounds with known product ion spectra using the measurement module by:
a) retrieving the known product ion spectra from a library,
b) 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 spectra,
c) generating product ion traces in time for the sample product ion spectra for one or more of the known product ion spectra,
d) calculating a score for the product ion traces and product ion spectra that represents how well known product ions of the known product ion spectra and sample product ions of the sample product ion spectra match, and e) calculating a quantitative value for the known compound from the product ion traces when the score exceeds a threshold value.

16. The computer p

Assignees

• Dh Technologies Dev Pte Ltd
• ETH Zürich

Inventors

• Bonner Ronald F
• Tate Stephen A
• Aebersold Rudolf
• Navarro Alvarez Pedro Jose
• Rinner Oliver
• Reiter Lukas
• Gillet Ludovic

Classifications

• G16C20/20

  Identification of molecular entities, parts thereof or of chemical compositions · CPC title

• G16C20/90

  Programming languages; Computing architectures; Database systems; Data warehousing · CPC title

• H01J49/0045

  characterised by the fragmentation or other specific reaction · CPC title

• H01J49/004

  Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn · CPC title

• H01J49/0036 Primary

  Step by step routines describing the handling of the data generated during a measurement · CPC title