Methods for time-alignment of liquid chromatography-mass spectrometry data

• US 20060131222A1
• Filed: 01/24/2006
• Published: 06/22/2006
• Est. Priority Date: 05/09/2002
• Status: Active Grant

• Current Assignee: Caprion Proteomics Inc. (CellCarta Biosciences, Inc.)
• Original Assignee: PPD Biomarker Discovery Sciences LLC (CellCarta Biosciences, Inc.)
• Inventors: Norton, Scott M.
• Granted Patent: US 7,628,914 B2
• Time in Patent Office: Days
• US Class Current: 210/198.200
• CPC Class Codes: G01N 30/7233 interfaced to liquid or supercritical fluid chromatograph interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04
• CPC Class Codes: G01N 30/8624 Detection of slopes or peaks; baseline correction
• CPC Class Codes: G01N 30/8631 Peaks
• CPC Class Codes: G01N 30/8644 Data segmentation, e.g. time windows
• CPC Class Codes: G01N 30/8668 using retention times
• CPC Class Codes: G06F 2218/12 Classification; Matching
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement

Abstract

Nonlinear retention time variations in chromatography-mass spectrometry data sets are adjusted by time-alignment methods, enabling automated comparison of spectra for differential phenotyping and other applications.

Claims

1. A plurality of chromatography-mass spectrometry data sets aligned according to a method comprising:

a) computing a distance function between said data sets in dependence on at least two mass chromatograms from each data set; and

b) aligning said data sets by minimizing said distance function to obtain aligned data sets.

2. A program storage device accessible by a processor, tangibly embodying a program of instructions executable by said processor to perform method steps for a method for time-aligning chromatography-mass spectrometry data sets, each comprising a plurality of mass chromatograms, said method steps comprising:

a) computing a distance function between said data sets in dependence on at least two mass chromatograms from each data set; and

b) aligning said data sets by minimizing said distance function to obtain aligned data sets.

3. A plurality of samples compared according to a method comprising:

a) performing chromatography-mass spectrometry on each sample to obtain at least two data sets, each comprising a plurality of mass chromatograms;

b) computing a distance function between two selected data sets in dependence on at least two mass chromatograms from each selected data set;

c) aligning said selected data sets by minimizing said distance function to obtain aligned selected data sets; and

d) comparing said aligned selected data sets.

4. A biomarker differentiating two cohorts identified by the method comprising:

a) comparing at least two samples, at least one each of said samples representing a different one of said two cohorts according to the method comprising;

i) performing chromatography-mass spectrometry on each sample to obtain at least two data sets, each comprising a plurality of mass chromatograms;

ii) computing a distance function between two selected data sets in dependence on at least two mass chromatograms from each selected data set;

iii) aligning said selected data sets by minimizing said distance function to obtain aligned selected data sets; and

iv) comparing said aligned selected data sets; and

b) identifying a biomarker in dependence on said comparison.

5. A plurality of chromatography-mass spectrometry data sets aligned according to a method comprising:

a) selecting peaks in said data sets;

b) identifying potentially corresponding peaks from said selected peaks; and

c) performing a locally-weighted regression smoothing on said potentially corresponding peaks to obtain aligned data sets.

6. A program storage device accessible by a processor, tangibly embodying a program of instructions executable by said processor to perform method steps for a method for time-aligning two-dimensional chromatography-mass spectrometry data sets, said method steps comprising:

a) selecting peaks in said data sets;

b) identifying potentially corresponding peaks from said selected peaks; and

c) performing a locally-weighted regression smoothing on said potentially corresponding peaks to obtain aligned data sets.

7. A plurality of samples compared according to a method comprising:

a) performing chromatography-mass spectrometry on each sample to obtain at least two two-dimensional data sets;

b) selecting peaks in two selected data sets;

c) identifying potentially corresponding peaks from said selected peaks;

d) performing a locally-weighted regression smoothing on said potentially corresponding peaks to obtain aligned selected data sets; and

e) comparing said aligned selected data sets.

8. A biomarker identified by the method comprising:

a) performing chromatography-mass spectrometry on each sample to obtain at least two two-dimensional data sets;

b) selecting peaks in two selected data sets;

c) identifying potentially corresponding peaks from said selected peaks;

d) performing a locally-weighted regression smoothing on said potentially corresponding peaks to obtain aligned selected data sets; and

e) comparing said aligned selected data sets.